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1.
Cell ; 159(4): 800-13, 2014 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-25417157

RESUMEN

We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes. Only 2% of the MSY derives from the ancestral autosomes that gave rise to the mammalian sex chromosomes. Instead, all but 45 of the MSY's genes belong to three acquired, massively amplified gene families that have no homologs on primate MSYs but do have acquired, amplified homologs on the mouse X chromosome. The complete mouse MSY sequence brings to light dramatic forces in sex chromosome evolution: lineage-specific convergent acquisition and amplification of X-Y gene families, possibly fueled by antagonism between acquired X-Y homologs. The mouse MSY sequence presents opportunities for experimental studies of a sex-specific chromosome in its entirety, in a genetically tractable model organism.


Asunto(s)
Evolución Biológica , Cromosomas de los Mamíferos , Ratones Endogámicos C57BL/genética , Análisis de Secuencia de ADN , Cromosoma Y , Animales , Centrómero , Cromosomas Artificiales Bacterianos/genética , Femenino , Humanos , Masculino , Filogenia , Primates/genética , Cromosoma X
2.
Semin Cell Dev Biol ; 163: 14-21, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38664120

RESUMEN

Chromosomal regions with meiotic drivers exhibit biased transmission (> 50 %) over their competing homologous chromosomal region. These regions often have two prominent genetic features: suppressed meiotic crossing over and rapidly evolving multicopy gene families. Heteromorphic sex chromosomes (e.g., XY) often share these two genetic features with chromosomal regions exhibiting meiotic drive. Here, we discuss parallels between meiotic drive and sex chromosome evolution, how the divergence of heteromorphic sex chromosomes can be influenced by meiotic drive, experimental approaches to study meiotic drive on sex chromosomes, and meiotic drive in traditional and non-traditional model organisms with high-quality genome assemblies. The newly available diversity of high-quality sex chromosome sequences allows us to revisit conventional models of sex chromosome evolution through the lens of meiotic drive.


Asunto(s)
Evolución Molecular , Meiosis , Cromosomas Sexuales , Meiosis/genética , Cromosomas Sexuales/genética , Animales , Humanos
3.
Cell Mol Life Sci ; 78(7): 3205-3218, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33449147

RESUMEN

Meiotic drive, the non-Mendelian transmission of chromosomes to the next generation, functions in asymmetric or symmetric meiosis across unicellular and multicellular organisms. In asymmetric meiosis, meiotic drivers act to alter a chromosome's spatial position in a single egg. In symmetric meiosis, meiotic drivers cause phenotypic differences between gametes with and without the driver. Here we discuss existing models of meiotic drive, highlighting the underlying mechanisms and regulation governing systems for which the most is known. We focus on outstanding questions surrounding these examples and speculate on how new meiotic drive systems evolve and how to detect them.


Asunto(s)
Evolución Biológica , Segregación Cromosómica , Meiosis , Huso Acromático/fisiología , Animales , Humanos
4.
Mol Biol Evol ; 37(7): 1979-1985, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32145018

RESUMEN

Large (>10 kb), nearly identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence of X-Y recombination. It is unclear whether X-palindromes, which can freely recombine in females, undergo arm-to-arm gene conversion and, if so, at what rate. We generated high-quality sequence assemblies of Mus molossinus and M. spretus X-palindromic regions and compared them with orthologous M. musculus X-palindromes. Our evolutionary sequence comparisons find evidence of X-palindrome arm-to-arm gene conversion at rates comparable to autosomal allelic gene conversion rates in mice. Mus X-palindromes also carry more derived than ancestral variants between species, suggesting that their sequence is rapidly diverging. We speculate that in addition to maintaining genes' sequence integrity via sequence homogenization, palindrome arm-to-arm gene conversion may also facilitate rapid sequence divergence.


Asunto(s)
Conversión Génica , Secuencias Invertidas Repetidas , Ratones/genética , Cromosoma X , Animales , Masculino , Especificidad de la Especie
5.
J Hered ; 111(5): 419-428, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32725191

RESUMEN

Reproductive isolation is a fundamental step in speciation. While sex chromosomes have been linked to reproductive isolation in many model systems, including hominids, genetic studies of the contribution of sex chromosome loci to speciation for natural populations are relatively sparse. Natural hybrid zones can help identify genomic regions contributing to reproductive isolation, like hybrid incompatibility loci, since these regions exhibit reduced introgression between parental species. Here, we use a primate hybrid zone (Alouatta palliata × Alouatta pigra) to test for reduced introgression of X-linked SNPs compared to autosomal SNPs. To identify X-linked sequence in A. palliata, we used a sex-biased mapping approach with whole-genome re-sequencing data. We then used genomic cline analysis with reduced-representation sequence data for parental A. palliata and A. pigra individuals and hybrids (n = 88) to identify regions with non-neutral introgression. We identified ~26 Mb of non-repetitive, putatively X-linked genomic sequence in A. palliata, most of which mapped collinearly to the marmoset and human X chromosomes. We found that X-linked SNPs had reduced introgression and an excess of ancestry from A. palliata as compared to autosomal SNPs. One outlier region with reduced introgression overlaps a previously described "desert" of archaic hominin ancestry on the human X chromosome. These results are consistent with a large role for the X chromosome in speciation across animal taxa and further, suggest shared features in the genomic basis of the evolution of reproductive isolation in primates.


Asunto(s)
Alouatta/genética , Genes Ligados a X , Genética de Población , Hibridación Genética , Aislamiento Reproductivo , Animales , Evolución Molecular , Femenino , Genoma , Genómica , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Cromosoma X
6.
Nucleic Acids Res ; 45(19): e165, 2017 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-28977642

RESUMEN

Megabase-sized, complex, repetitive regions of genomes are poorly studied, due to the technical and computational challenges inherent to both assembling precise reference sequences and accurately assessing structural variation across contiguous megabase DNA regions. Here we describe a strategy to overcome these challenges, CISMR (CRISPR-mediated isolation of specific megabase-sized regions of the genome), which enables us to perform targeted isolation of contiguous megabase-sized segments of the genome. Direct sequencing of the purified DNA segments can have >100-fold enrichment of the target region, thus enabling the exploration of both DNA sequence and structural diversity of complex genomic regions in any species.


Asunto(s)
Sistemas CRISPR-Cas , ADN/genética , Genoma/genética , Animales , ADN/aislamiento & purificación , ADN de Hongos/genética , Electroforesis en Gel de Campo Pulsado/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ratones , Reproducibilidad de los Resultados , Saccharomyces cerevisiae/genética
7.
PLoS Genet ; 11(9): e1005531, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26378784

RESUMEN

The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. By profiling gene expression in the mouse fetal ovary in mutants with whole tissue and single-cell techniques, we identified 104 genes expressed specifically in pre-meiotic to pachytene germ cells. We characterized the regulation of these genes by 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase. Initial induction of practically all identified meiotic prophase genes requires Dazl. In the presence of Dazl, RA induces at least two pathways: one Stra8-independent, and one Stra8-dependent. Genes vary in their induction by Stra8, spanning fully Stra8-independent, partially Stra8-independent, and fully Stra8-dependent. Thus, Stra8 regulates the entirety of the chromosomal program but plays a more nuanced role in governing the gene expression program. We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of meiotic prophase, and ensure that it is induced only once.


Asunto(s)
Redes Reguladoras de Genes , Profase Meiótica I , Ovario/embriología , Ovinos/embriología , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Regulación hacia Abajo , Femenino , Regulación del Desarrollo de la Expresión Génica , Ovario/citología
8.
PLoS One ; 19(6): e0303577, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38843233

RESUMEN

Malic Enzyme 1 (ME1) plays an integral role in fatty acid synthesis and cellular energetics through its production of NADPH and pyruvate. As such, it has been identified as a gene of interest in obesity, type 2 diabetes, and an array of epithelial cancers, with most work being performed in vitro. The current standard model for ME1 loss in vivo is the spontaneous Mod-1 null allele, which produces a canonically inactive form of ME1. Herein, we describe two new genetically engineered mouse models exhibiting ME1 loss at dynamic timepoints. Using murine embryonic stem cells and Flp/FRT and Cre/loxP class switch recombination, we established a germline Me1 knockout model (Me1 KO) and an inducible conditional knockout model (Me1 cKO), activated upon tamoxifen treatment in adulthood. Collectively, neither the Me1 KO nor Me1 cKO models exhibited deleterious phenotype under standard laboratory conditions. Knockout of ME1 was validated by immunohistochemistry and genotype confirmed by PCR. Transmission patterns favor Me1 loss in Me1 KO mice when maternally transmitted to male progeny. Hematological examination of these models through complete blood count and serum chemistry panels revealed no discrepancy with their wild-type counterparts. Orthotopic pancreatic tumors in Me1 cKO mice grow similarly to Me1 expressing mice. Similarly, no behavioral phenotype was observed in Me1 cKO mice when aged for 52 weeks. Histological analysis of several tissues revealed no pathological phenotype. These models provide a more modern approach to ME1 knockout in vivo while opening the door for further study into the role of ME1 loss under more biologically relevant, stressful conditions.


Asunto(s)
Malato Deshidrogenasa , Ratones Noqueados , Fenotipo , Animales , Malato Deshidrogenasa/metabolismo , Malato Deshidrogenasa/genética , Masculino , Ratones , Femenino , Células Germinativas/metabolismo , Ratones Endogámicos C57BL
9.
Am J Hum Genet ; 97(4): 507-10, 2015 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-26713337
10.
Sci Rep ; 12(1): 8554, 2022 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-35595785

RESUMEN

Mammalian sex chromosomes are enriched for large, nearly-identical, palindromic sequences harboring genes expressed predominately in testicular germ cells. Discerning if individual palindrome-associated gene families are essential for male reproduction is difficult due to challenges in disrupting all copies of a gene family. Here we generate precise, independent, deletions to assess the reproductive roles of two X-linked palindromic gene families with spermatid-predominant expression, 4930567H17Rik and Mageb5. Sequence analyses reveals mouse 4930567H17Rik and Mageb5 are orthologs of human HSFX3 and MAGEB5, respectively, where 4930567H17Rik/HSFX3 is harbored in a palindrome in humans and mice, while Mageb5 is not. Additional sequence analyses show 4930567H17Rik and HSFX3 are rapidly diverging in rodents and primates, respectively. Mice lacking either 4930567H17Rik or Mageb5 gene families do not have detectable defects in male fertility, fecundity, spermatogenesis, or in gene regulation, but do show differences in sperm head morphology, suggesting a potential role in sperm function. We conclude that while all palindrome-associated gene families are not essential for male fertility, large palindromes influence the evolution of their associated gene families.


Asunto(s)
Cromosomas Sexuales , Espermatogénesis , Animales , Fertilidad/genética , Masculino , Mamíferos/genética , Ratones , Espermatogénesis/genética , Espermatozoides , Testículo/metabolismo
11.
G3 (Bethesda) ; 10(6): 1997-2005, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32253194

RESUMEN

Mouse sex chromosomes are enriched for co-amplified gene families, present in tens to hundreds of copies. Co-amplification of Slx/Slxl1 on the X chromosome and Sly on the Y chromosome are involved in dose-dependent meiotic drive, however the role of other co-amplified genes remains poorly understood. Here we demonstrate that the co-amplified gene family on the X chromosome, Srsx, along with two additional partial gene annotations, is actually part of a larger transcription unit, which we name LaidxLaidx is harbored in a 229 kb amplicon that represents the ancestral state as compared to a 525 kb Y-amplicon containing the rearranged LaidyLaidx contains a 25,011 nucleotide open reading frame, predominantly expressed in round spermatids, predicted to encode an 871 kD protein. Laidx has orthologous copies with the rat and also the 825-MY diverged parasitic Chinese liver fluke, Clonorchis sinensis, the likely result of a horizontal gene transfer of rodent Laidx to an ancestor of the liver fluke. To assess the male reproductive functions of Laidx, we generated mice carrying a multi-megabase deletion of the Laidx-ampliconic region. Laidx-deficient male mice do not show detectable reproductive defects in fertility, fecundity, testis histology, and offspring sex ratio. We speculate that Laidx and Laidy represent a now inactive X vs. Y chromosome conflict that occurred in an ancestor of present day mice.


Asunto(s)
Proteínas Intrínsecamente Desordenadas , Animales , Genómica , Masculino , Ratones , Ratas , Espermátides , Cromosoma X/genética , Cromosoma Y/genética
12.
Genetics ; 178(3): 1605-14, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18245332

RESUMEN

Internally fertilizing organisms transfer a complex assortment of seminal fluid proteins, a substantial fraction of which are proteolysis regulators. In mammals, some seminal protease inhibitors have been implicated in male infertility and these same molecular classes of protease inhibitors are also found in Drosophila seminal fluid. Here, we tested the reproductive functions of the Drosophila melanogaster seminal fluid protease inhibitor Acp62F by generating a precise deletion of the Acp62F gene. We did not detect a nonredundant function for Acp62F in modulating the egg laying, fertility, remating frequency, or life span of mated females. However, loss of Acp62F did alter a male's defensive sperm competitive ability, consistent with the localization of Acp62F to sperm storage organs. In addition, the processing of at least one seminal protein, the ovulation hormone ovulin, is slower in the absence of Acp62F.


Asunto(s)
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Eliminación de Gen , Marcación de Gen , Inhibidores de Proteasas/metabolismo , Semen/metabolismo , Proteínas de Plasma Seminal/genética , Alelos , Animales , Western Blotting , Proteínas de Drosophila/metabolismo , Femenino , Fertilidad , Péptidos y Proteínas de Señalización Intercelular , Longevidad , Masculino , Oviposición , Péptidos/metabolismo , Fenotipo , Procesamiento Proteico-Postraduccional , Proteínas de Plasma Seminal/metabolismo , Conducta Sexual Animal , Espermatozoides/metabolismo , Análisis de Supervivencia
13.
Curr Biol ; 29(21): 3699-3706.e5, 2019 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-31630956

RESUMEN

The mammalian sex chromosomes harbor an abundance of newly acquired ampliconic genes, although their functions require elucidation [1-9]. Here, we demonstrate that the X-linked Slx and Slxl1 ampliconic gene families represent mouse-specific neofunctionalized copies of a meiotic synaptonemal complex protein, Sycp3. In contrast to the meiotic role of Sycp3, CRISPR-loxP-mediated multi-megabase deletions of the Slx (5 Mb) and Slxl1 (2.3Mb) ampliconic regions result in post-meiotic defects, abnormal sperm, and male infertility. Males carrying Slxl1 deletions sire more male offspring, whereas males carrying Slx and Slxl1 duplications sire more female offspring, which directly correlates with Slxl1 gene dosage and gene expression levels. SLX and SLXL1 proteins interact with spindlin protein family members (SPIN1 and SSTY1/2) and males carrying Slxl1 deletions downregulate a sex chromatin modifier, Scml2, leading us to speculate that Slx and Slxl1 function in chromatin regulation. Our study demonstrates how newly acquired X-linked genes can rapidly evolve new and essential functions and how gene amplification can increase sex chromosome transmission.


Asunto(s)
Fertilidad/genética , Genes Ligados a X/genética , Familia de Multigenes/genética , Cromosomas Sexuales/genética , Razón de Masculinidad , Animales , Femenino , Dosificación de Gen , Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA
14.
Genetics ; 175(2): 777-83, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17110486

RESUMEN

In Drosophila melanogaster, seminal fluid regulates the reproductive and immune responses of mated females. Some seminal fluid proteins may provide protective functions to mated females, such as antimicrobial activity and/or stimulation of antimicrobial gene expression levels, while others appear to have negative effects, contributing to a "cost of mating." To identify seminal proteins that could participate in these phenomena, we used a systemic ectopic expression screen to test the effects on unmated females of proteins normally produced by the male accessory gland (Acps). Of the 21 ectopically expressed Acps that we tested for ability to assist in the clearance of a bacterial infection with Serratia marcescens, 3 Acps significantly reduced the bacterial counts of infected females, suggesting a protective role. Of the 23 Acps that we tested for toxicity, 3 were toxic, including one that has been implicated in the cost of mating in another study. We also tested ectopic expression females for other Acp-induced effects, but found no additional Acps that affected egg laying or receptivity upon ectopic expression.


Asunto(s)
Proteínas de Drosophila/farmacología , Proteínas de Drosophila/toxicidad , Drosophila melanogaster/efectos de los fármacos , Expresión Génica , Proteínas de Plasma Seminal/farmacología , Proteínas de Plasma Seminal/toxicidad , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/microbiología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Oviposición/efectos de los fármacos , Proteínas de Plasma Seminal/genética , Proteínas de Plasma Seminal/metabolismo , Infecciones por Serratia , Serratia marcescens/efectos de los fármacos , Serratia marcescens/crecimiento & desarrollo , Abstinencia Sexual/efectos de los fármacos , Conducta Sexual Animal/efectos de los fármacos
15.
Sci Rep ; 8(1): 8985, 2018 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-29895860

RESUMEN

Large (>10 kb) palindromic sequences are enriched on mammalian sex chromosomes. In mice, these palindromes harbor gene families (≥2 gene copies) expressed exclusively in post-meiotic testicular germ cells, a time when most single-copy sex-linked genes are transcriptionally repressed. This observation led to the hypothesis that palindromic structures or having ≥2 gene copies enable post-meiotic gene expression. We tested these hypotheses by using CRISPR to precisely engineer large (10's of kb) inversions and deletions of X-chromosome palindrome arms for two regions that carry the mouse 4930567H17Rik and Mageb5 palindrome gene families. We found that 4930567H17Rik and Mageb5 gene expression is unaffected in mice carrying palindrome arm inversions and halved in mice carrying palindrome arm deletions. We assessed whether palindrome-associated genes were sensitive to reduced expression in mice carrying palindrome arm deletions. Male mice carrying palindrome arm deletions are fertile and show no defects in post-meiotic spermatogenesis. Together, these findings suggest palindromic structures on the sex chromosomes are not necessary for their associated genes to evade post-meiotic transcriptional repression and that these genes are not sensitive to reduced expression levels. Large sex chromosome palindromes may be important for other reasons, such as promoting gene conversion between palindrome arms.


Asunto(s)
Deleción Cromosómica , Inversión Cromosómica , Regulación de la Expresión Génica , Secuencias Invertidas Repetidas , Meiosis , Cromosoma X , Animales , Masculino , Ratones , Cromosoma X/genética , Cromosoma X/metabolismo
16.
Genetics ; 172(2): 1093-105, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16322515

RESUMEN

Drosophila melanogaster originated in tropical Africa but has achieved a cosmopolitan distribution in association with human habitation. Cosmopolitan populations of D. melanogaster are known to have reduced genetic variation, particularly on the X chromosome. However, the relative importance of population bottlenecks and selective sweeps in explaining this reduction is uncertain. We surveyed variation at 31 microsatellites across a 330-kb section of the X chromosome located between the white and kirre genes. Two linked clusters of loci were observed with reduced variation and a skew toward rare alleles in both an Ecuador and a Zimbabwe population sample. Examining Zimbabwe DNA sequence polymorphism within one of these regions allowed us to localize a selective sweep to a 361-bp window within the 5' regulatory region of the roughest gene, with one nucleotide substitution representing the best candidate for the target of selection. Estimates of sweep age suggested that this fixation event occurred prior to the expansion of D. melanogaster from sub-Saharan Africa. For both putative sweep regions in our data set, cosmopolitan populations showed wider footprints of selection compared to those in Zimbabwe. This pattern appears consistent with the demographic amplification of preexisting sweep signals due to one or more population bottlenecks.


Asunto(s)
Drosophila melanogaster/genética , Variación Genética , Genética de Población , Animales , Repeticiones de Dinucleótido , Ecuador , Datos de Secuencia Molecular , Polimorfismo Genético , Zimbabwe
17.
Nat Biotechnol ; 20(11): 1118-23, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12368813

RESUMEN

Shewanella oneidensis is an important model organism for bioremediation studies because of its diverse respiratory capabilities, conferred in part by multicomponent, branched electron transport systems. Here we report the sequencing of the S. oneidensis genome, which consists of a 4,969,803-base pair circular chromosome with 4,758 predicted protein-encoding open reading frames (CDS) and a 161,613-base pair plasmid with 173 CDSs. We identified the first Shewanella lambda-like phage, providing a potential tool for further genome engineering. Genome analysis revealed 39 c-type cytochromes, including 32 previously unidentified in S. oneidensis, and a novel periplasmic [Fe] hydrogenase, which are integral members of the electron transport system. This genome sequence represents a critical step in the elucidation of the pathways for reduction (and bioremediation) of pollutants such as uranium (U) and chromium (Cr), and offers a starting point for defining this organism's complex electron transport systems and metal ion-reducing capabilities.


Asunto(s)
Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Análisis de Secuencia de ADN , Análisis de Secuencia de Proteína , Shewanella/genética , Shewanella/metabolismo , Secuencia de Aminoácidos , Biodegradación Ambiental , Respiración de la Célula , Transporte de Electrón , Expresión Génica , Metales/metabolismo , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Compuestos Orgánicos/metabolismo , Oxidación-Reducción , Plásmidos , Proteómica/métodos , Alineación de Secuencia/métodos , Shewanella/clasificación , Shewanella/patogenicidad , Especificidad de la Especie , Contaminantes Químicos del Agua/metabolismo , Purificación del Agua/métodos
18.
Int J Sports Phys Ther ; 12(5): 774-786, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29181255

RESUMEN

INTRODUCTION: Dysfunctional breathing (DB) has been linked to health conditions including low back pain and neck pain and adversely effects the musculoskeletal system. Individuals with DB often have decreased pain thresholds and impaired motor control, balance, and movement. No single test or screen identifies DB, which is multi-dimensional, and includes biochemical, biomechanical, and psychophysiological components. Several tools assess and test for DB, but no screen exists to determine whether additional testing and assessment are indicated. PURPOSE/BACKGROUND: The purpose of this study was to develop a breathing screening procedure that could be utilized by fitness and healthcare providers to screen for the presence of disordered breathing. A diagnostic test study approach was utilized to establish the diagnostic accuracy of the newly developed screen for DB. METHODS: A convenience sample of 51 subjects (27 females, 27.0 years, BMI 23.3) were included. To test for DB related to the biochemical dimension, end-tidal CO2 (ETCO2) was measured with a capnography unit. To test for DB related to biomechanical dimension, the Hi-Lo test was utilized. To test for DB related to the psychophysiological dimension, the Self Evaluation of Breathing Symptoms Questionnaire (SEBQ) and Nijmegen questionnaires were utilized. Potential screening items that have been shown to be related to DB in previous research and that could be performed by non-health care personnel were utilized to create the index test including activity level, breath hold time (BHT), respiration rate, and the Functional Movement Screen (FMS™). RESULTS: There were no strong correlations between the three measures of DB. Five subjects had normal breathing, 14 failed at least one measure, 20 failed at least two, and 12 failed all three. To develop screening items for each dimension, data were examined for association with failure. BHT and a four-item mini-questionnaire were identified as the most closely associated variables with failure of all three dimensions. A BHT of < 25 seconds and four questions were combined and yielded a sensitivity of 0.89 (0.85-0.93) and a specificity of 0.60 (0.18-0.92) for clinical identification of DB. CONCLUSION: Easily obtained clinical measures of BHT and four questions can be utilized to screen for the presence of DB. If the screen is passed, there is an 89% chance that DB is not present. If the screen is failed, further assessment is recommended. LEVEL OF EVIDENCE: 2b.

19.
Nat Genet ; 45(9): 1083-7, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23872635

RESUMEN

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. 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.


Asunto(s)
Células Germinativas/metabolismo , Cromosoma X/genética , Animales , Mapeo Cromosómico , Biología Computacional , Evolución Molecular , Genes Ligados a X , Genómica , Humanos , Masculino , Mamíferos/genética , Ratones , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Cromosoma X/química
20.
Nat Genet ; 40(6): 794-9, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18454149

RESUMEN

According to the prevailing view, mammalian X chromosomes are enriched in spermatogenesis genes expressed before meiosis and deficient in spermatogenesis genes expressed after meiosis. The paucity of postmeiotic genes on the X chromosome has been interpreted as a consequence of meiotic sex chromosome inactivation (MSCI)--the complete silencing of genes on the XY bivalent at meiotic prophase. Recent studies have concluded that MSCI-initiated silencing persists beyond meiosis and that most genes on the X chromosome remain repressed in round spermatids. Here, we report that 33 multicopy gene families, representing approximately 273 mouse X-linked genes, are expressed in the testis and that this expression is predominantly in postmeiotic cells. RNA FISH and microarray analysis show that the maintenance of X chromosome postmeiotic repression is incomplete. Furthermore, X-linked multicopy genes exhibit a similar degree of expression as autosomal genes. Thus, not only is the mouse X chromosome enriched for spermatogenesis genes functioning before meiosis, but in addition, approximately 18% of mouse X-linked genes are expressed in postmeiotic cells.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Genes Ligados a X/genética , Espermatogénesis/genética , Espermatozoides/metabolismo , Testículo/fisiología , Cromosoma X/genética , Animales , Sondas de ADN , Dosificación de Gen , Hibridación Fluorescente in Situ , Masculino , Meiosis/genética , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Sondas ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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