Genetic Monitoring

Fox, R. R.; Wiles, Michael V.; Petkov, Petko M.

doi:10.1016/b978-012369454-6/50020-0

Cited by 16 publications

(19 citation statements)

References 17 publications

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“…The wealth of new insight gained about the genetic and cellular underpinnings of biology might be argued as justification for this relegation of the comparative anatomical sciences, and their associated museum collections, to the disciplinary sidelines. However, because developmental genetics today aims for a genotype/phenotype map that can inform us about our own species' biology, the many millions of years of evolution that stand between H. sapiens and mice still pose a formidable hurdle (8,9,45). We report here that considerable progress for identifying GP skeletal phenotypes beyond the mouse model is possible through transdisciplinary approaches that include the anatomical sciences.…”

Section: Discussionmentioning

confidence: 99%

“…This research has been advanced significantly by the revolution in developmental genetics over the past few decades (7). Experimental research on mice has yielded tremendous biological insight (8). However, for human phenotypes, ranging from inflammation (9) to placentation (10), the limitations of the mouse model due to the ∼140 million years ago of evolution that have occurred since our last common ancestor ∼70 Ma (11) are starting to be recognized.…”

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confidence: 99%

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The integration of quantitative genetics, paleontology, and neontology reveals genetic underpinnings of primate dental evolution

Hlusko

Schmitt

Monson

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

107

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Developmental genetics research on mice provides a relatively sound understanding of the genes necessary and sufficient to make mammalian teeth. However, mouse dentitions are highly derived compared with human dentitions, complicating the application of these insights to human biology. We used quantitative genetic analyses of data from living nonhuman primates and extensive osteological and paleontological collections to refine our assessment of dental phenotypes so that they better represent how the underlying genetic mechanisms actually influence anatomical variation. We identify ratios that better characterize the output of two dental genetic patterning mechanisms for primate dentitions. These two newly defined phenotypes are heritable with no measurable pleiotropic effects. When we consider how these two phenotypes vary across neontological and paleontological datasets, we find that the major Middle Miocene taxonomic shift in primate diversity is characterized by a shift in these two genetic outputs. Our results build on the mouse model by combining quantitative genetics and paleontology, and thereby elucidate how genetic mechanisms likely underlie major events in primate evolution.paleontology | quantitative genetics | primates | neontology | dental variation T he relationship between genotype and phenotype is critical to evolutionary biology, because it influences how phenotypes respond to selective pressures and evolve (1, 2). Paleontologists have long sought to incorporate the etiology of the dental phenotype to inform on questions of environmental, dietary, and adaptive change over time (3)(4)(5)(6). This research has been advanced significantly by the revolution in developmental genetics over the past few decades (7). Experimental research on mice has yielded tremendous biological insight (8). However, for human phenotypes, ranging from inflammation (9) to placentation (10), the limitations of the mouse model due to the ∼140 million years ago of evolution that have occurred since our last common ancestor ∼70 Ma (11) are starting to be recognized. Here, we demonstrate how to overcome the limitations of the mouse model's application to the primate dentition by integrating research from quantitative genetics, neontology, and paleontology. The insights gained from this transdisciplinary approach have implications for all of these seemingly disparate subdisciplines of biology.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The integration of quantitative genetics, paleontology, and neontology reveals genetic underpinnings of primate dental evolution

Hlusko

Schmitt

Monson

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

107

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“…iHR and mHR were determined from ECGs recorded from awake, restrained mice of three age groups: 2-3, 21-24, and 32+ mo (corresponding to ∼17-20, 65-69, and 87+ y in humans) (30,31) (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Larson

Clair

Sumner

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

113

163

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An inexorable decline in maximum heart rate (mHR) progressively limits human aerobic capacity with advancing age. This decrease in mHR results from an age-dependent reduction in "intrinsic heart rate" (iHR), which is measured during autonomic blockade. The reduced iHR indicates, by definition, that pacemaker function of the sinoatrial node is compromised during aging. However, little is known about the properties of pacemaker myocytes in the aged sinoatrial node. Here, we show that depressed excitability of individual sinoatrial node myocytes (SAMs) contributes to reductions in heart rate with advancing age. We found that agedependent declines in mHR and iHR in ECG recordings from mice were paralleled by declines in spontaneous action potential (AP) firing rates (FRs) in patch-clamp recordings from acutely isolated SAMs. The slower FR of aged SAMs resulted from changes in the AP waveform that were limited to hyperpolarization of the maximum diastolic potential and slowing of the early part of the diastolic depolarization. These AP waveform changes were associated with cellular hypertrophy, reduced current densities for L-and T-type Ca 2+ currents and the "funny current" (I f ), and a hyperpolarizing shift in the voltage dependence of I f . The agedependent reduction in sinoatrial node function was not associated with changes in β-adrenergic responsiveness, which was preserved during aging for heart rate, SAM FR, L-and T-type Ca 2+ currents, and I f . Our results indicate that depressed excitability of individual SAMs due to altered ion channel activity contributes to the decline in mHR, and thus aerobic capacity, during normal aging. O ne of the most insidious aspects of growing older is an inevitable decline in maximum heart rate (mHR), which limits maximum aerobic capacity with advancing age (1-3). The decline in mHR proceeds at approximately the same rate for all individuals, without regard for lifestyle or physical fitness (4-8). For many otherwise healthy elderly people, it is the factor that ultimately restricts the ability to live independently (9, 10).The decrease in mHR with age results primarily from a parallel age-dependent decline in "intrinsic heart rate" (iHR) (11-13), which is measured during autonomic blockade, and thus reflects the spontaneous pacemaker activity of the sinoatrial node of the heart. Although it is known that the intact sinoatrial node from aged animals contracts more slowly (14, 15) and contains fewer pacemaker myocytes (16), little is known about the functional properties of individual myocytes from the sinoatrial node of the aged heart.Sinoatrial myocytes (SAMs) are highly specialized cells that serve a primarily electrical function as cardiac pacemakers via their production of spontaneous action potentials (APs). Sinoatrial APs are characterized by a spontaneous depolarization during diastole that drives the membrane potential to threshold, thereby triggering the subsequent AP. This "diastolic depolarization" (DD) phase of the sinoatrial AP results from the coordinated activit...

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“…MRV is likely related to the previously described MTV, a naturally occurring mouse herpesvirus (3,35). MTV was originally identified by assaying tissue homogenates for viruses that drive mammary tumorigenesis (19).…”

Section: Discussionmentioning

confidence: 99%

“…MCMV and ␥HV68 are clearly related to their human counterparts by sequence homology. Moreover, they share common mechanisms of pathogenesis and their homologous genes (3,16,17) exhibit similar functions. For instance, MCMV infection recapitulates most aspects of HCMV disease, with the exception of congenital infection due to the lack of placental infection (18).…”

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confidence: 99%

A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion

Patel

Zhao

Penna

et al. 2017

J Virol

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The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4 ϩ T cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By next-generation sequencing of infected tissue homogenates, we assembled a contiguous 174-kb genome sequence containing 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV-6A, HHV-6B, and HHV-7, than to another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV-6A, HHV-6B, and HHV-7.IMPORTANCE Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesviruses 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and clinical ramifications of roseolovirus infection in humans have been hypothesized, but studies showing definitive causative relationships between infection and disease susceptibility are lacking. Here we show that MRV infects the thymus and causes T-cell depletion, suggesting that other roseoloviruses may have similar properties.KEYWORDS herpesviruses, roseolovirus T he study of herpesviruses has been fruitful, not only revealing mechanisms that drive disease but also providing insight into diverse processes, including oncogenesis and immune regulation (1). The Herpesviridae family includes several highly prevalent human pathogens (1-3). While they are related, these viruses have diverse genomes,

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Genetic Monitoring

Cited by 16 publications

References 17 publications

The integration of quantitative genetics, paleontology, and neontology reveals genetic underpinnings of primate dental evolution

The integration of quantitative genetics, paleontology, and neontology reveals genetic underpinnings of primate dental evolution

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion

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