Thomas Gehrig, MD

• Cardiology Fellow
• Division of Cardiovascular Medicine
• Duke University Medical Center
• Durham, North Carolina

Rearing effects on cerebrospinal fluid oxytocin concentration and social buffering in rhesus monkeys hypertension screening icd 9 buy cheap exforge 80mg online. Transgenerational transmission of a stress-coping phenotype programmed by early-life stress in the Japanese quail arrhythmia beta blockers generic exforge 80 mg on line. Like all other life forms prehypertension a literature-documented public health concern cheap 80 mg exforge visa, we are evolved creatures arrhythmias definition cheap 80mg exforge overnight delivery, the product of both genes and our environments (see Chapter 1) blood pressure for heart attack buy exforge us. Instead hypertension and obesity order generic exforge, resistance lies in the way that genetic and biological processes are theorized, studied and interpreted in the human context. Similar objections are made to the application of evolutionary theory to modern humans (although there is no apparent problem applying it to the extinct versions of our genus). Again, there is a general acceptance that humans are evolved creatures while, at the same time, there is entrenched resistance to the idea that evolutionary processes influence contemporary human behaviour. At least some of this resistance reflects the way that evolutionary thinking has been applied to humans, rather than resistance to evolutionary thinking itself. In both cases, there remains a worry that labelling a trait or behaviour as genetic/biological or evolved is to suggest that it is immutable and predetermined. There is a distinction to be made between the two, however: talk of a genetic influence on behaviour does not, in itself, imply any kind of adaptive evolutionary explanation (or indeed any evolutionary explanation at all). Discussions of the value of evolutionary thinking as applied to humans thus address a different set of issues to those concerning the value of genetic studies of humans, including behavioural genetics. Instead, behavioural genetics is concerned with the extent to which variance in a trait across people can be attributed to genetic versus environmental differences, and what such differences might mean. In our view, the persistence of the nature-nurture debate into the twenty-first century often has more to do with a misunderstanding of the aims of behavioural genetic studies than with the application of evolutionary theory to humans in a broader sense. Consequently, in what follows, we first discuss briefly why studies in behavioural genetics seem to fuel the nature-nurture debate. We then go on to consider how evolutionary thinking can help improve our understanding of human behaviour, as well as showing why non-evolutionary thinking can sometimes go awry. Note that we make no attempt to be comprehensive in our assessment, rather we use a few key examples to illustrate the value of evolutionary thinking to real-world issues. The reasons for this can be found in its origins in animal breeding and crop domestication. Artificial selection requires an accurate assessment of the likely response to controlled breeding; if most of the differences between individuals reflect variation in the environmental conditions encountered during growth and development, then artificial selection may prove ineffectual at producing a (suite of) desired trait(s). Hence, experimental and analytical techniques were developed that could partition the variance across individuals into its genetic and environmental components, enabling an assessment of the likely response to selection. Fisher himself made clear, an inconvenience that can either be ignored (if the effect is very small) or else transformed to meet linear expectations (Fisher and Mackenzie 1923). This stands in contrast to the views of evolutionary developmentalists and geneticists, who are interested in the causal mechanisms that produce traits, and thus consider interactions between genes, gene products, the cellular environment and the broader ecological (and, in the case of humans, socio-economic) environment as both fundamental and central to any understanding of how a given gene might exert its effects (Tabery 2014). That is, we can view all genes as potential difference makers, but only some will make an actual difference to the actual differences seen across individuals. Partitioning the variance then gives us some idea of whether the difference maker has been identified, whether we have identified a difference among many difference makers, or whether the difference made depends on environmental context. Once identified, actual difference makers can be studied by evolutionary developmentalists who seek to understand the causal mechanisms by which differences across individuals are produced. This represents a misunderstanding, if not an outright distortion, of an evolutionary approach, not least because the interactive process of development requires that organisms inherit certain stable features of their environment in addition to genes. Given this, it makes no sense to insist that behaviour can be driven by genes alone, particularly not in large multicellular animals like ourselves. It is also important to note that demonstrating that a current behaviour is fitness enhancing. It is also the case that, even if one can demonstrate natural selection phenotypically. The size of the effect was, however, very small, making it highly unlikely that natural selection alone explains much of the startling 20 cm increase in height shown by the Dutch over the past century (Stulp et al. In addition, there was no evidence presented to support a genetic response to selection. What was apparent, however, was that the small effect of natural selection is acting in concert with the environmental conditions that promote increased height. Thus, even when effects are small, it is possible that they can help explain differences in trait values across different populations (Stulp and Barrett 2016). Finally, the fact that social and cultural practices are themselves inherited and undergo transformation (see Chapter 3), and interact with genetic evolution, can make human evolutionary processes subject to more complex evolutionary dynamics (Richerson and Boyd 2005; Henrich and McElreath 2003). Evolutionary analyses must therefore be conducted with care, and interpreted cautiously, especially as ethical concerns mean that confirmatory experiments cannot be conducted. One way is that it can help make sense of findings that would otherwise seem counterintuitive or puzzling. Agricultural lifestyles are associated with sedenterization, food storage, wealth accumulation and increased population growth (Piperno and Pearsall 1998; Price and Gebauer 1995). At the same time, the shift from hunting and gathering to sedenterization and cultivation demonstrably resulted in poorer health and increased mortality, as revealed by reductions in stature, poorer oral health, and evidence of diseases, such as tuberculosis, plague and syphilis (Cohen and Crane-Kramer 2007). Why then did agriculture succeed in replacing hunting and gathering lifestyles given that it poses a much greater threat to survival The short, and flippant, answer is that natural selection does not care about health, only fitness. This is offset, however, by an increased reproductive rate, due to the energy savings that result from a more settled lifestyle. This results in a larger number of surviving offspring for settled compared to hunting and gathering Agta. Thus, the invention and adoption of agriculture, as a cultural trait, is argued to have selected for a faster life history strategy, resulting in agriculturalists outcompeting hunter-gatherers, which in turn helped increase the spread of agriculture via a process of intertwined cultural and biological evolution. Applying an explicitly evolutionary perspective can thus help explain the otherwise counterintuitive spread of a behaviour that actively reduced the health and well-being of those who practised it. Despite this, the practice remains widespread in many areas of Africa and the Middle East (where its prevalence ranges from 1% to 99%), and continues in the face of concerted and long-standing political efforts to eradicate it (Howard and Gibson 2017). One suggestion why eradication is so difficult is that cultural evolutionary processes take precedence here, promoting a behaviour that would otherwise fail to persist given its apparent negative biological fitness consequences for individuals. It is not simply the case that a strange and harmful idea has somehow become entrenched, persisting despite its fitness costs. Gibson and Mace (2006) provide one such example, with respect to the provision of labour-saving wells. Much like the Agta example described above, reduced workloads would automatically translate into more energy available for reproduction and, in the absence of reliable contraception, larger families. Their study focused on a rural agro-pastoralist community in Arsi, southern Ethiopia, which suffered from both regular water shortages and food insecurity. During the driest months of the year, this reduced the amount of time women spent carrying water from just over three hours to only 15 minutes per day. As predicted, women with access to taps were three times more likely to give birth in any given month relative to women without access, and water access was also associated with a 50% lower risk of children dying. Although the intervention was successful at reducing child mortality, it came at the cost of increasing childhood malnutrition. Gibson and Mace (2006) suggest this latter effect could be due to increased sibling competition for limited resources (as seen in other studies, such as Lawson and Mace 2009) or, perhaps more likely, as a consequence of reduced mortality among low-birthweight babies (which, potentially, could represent a relaxation of selection on low birthweight, if such a trait were heritable). The effects of malnutrition were seen only in the children born following tap installation, rather than across all age groups, suggesting that improved water access increased the likelihood of low-birthweight babies coming to full term and surviving critical early periods of childhood. Another example of a potentially misapplied intervention is the fortification with iron of infant milk formula. Infant iron stores are largely accumulated over the course of gestation, and decline in the first few months post partum in breast-fed infants, as human milk is low in iron (0. This decline generally has been viewed as pathological, thus resulting in a debate over the appropriate amount of iron fortification in infant formula: this can range from 4 to 12 mg l-1, so even the lowest levels are an order of magnitude higher than those found in breast milk. Quinn (2014) has suggested that we have things the wrong way around, and high levels of fortification may, in fact, be pathological. Her hypothesis is that iron depletion over the course of early life is an adaptive response to the onset of weaning and the introduction of non-milk foods. Many bacteria require iron for growth and replication, so low iron levels may limit the duration and severity of any infection to which an infant is exposed during the introduction of solid foods. Selection may thus have favoured mothers who produced low-iron milk, along with offspring with decreased iron stores at weaning, as this would increase the chance of surviving the weaning period. Although we currently lack the data needed to fully test this hypothesis, Quinn (2014) cites data from a number of studies demonstrating that low levels of iron intake during infancy were not associated with higher levels of anaemia and, in one study, low levels of iron were associated with both lower rates of infection and greater head growth. Contemporary fortification practices may therefore undermine these adaptive mechanisms, and increase the chances of children falling ill, rather than providing them with a health-giving boost. The application of an evolutionary perspective thus helps makes sense of why technological developments aimed at improving maternal and infant quality of life can backfire potentially. This often strikes people as rather odd, given that the availability of reliable contraception has been given as a reason why people no longer maximize their fitness in modern, industrial societies. Natural fertility populations can and do practise fertility control (but often with less reliable methods than the contraceptive pill) and there is widespread evidence for the use of contraception and abortifacients reaching all the way back to antiquity (Colleran and Mace 2015; McLaren 1990; Riddle 1994). Attempting to control fertility should not, therefore, automatically be seen as a break between sex and procreation, rendering evolutionary explanations irrelevant. The existence of fundamental trade-offs between investment in continued reproduction and investment in other domains, such as growth, bodily maintenance and care of existing offspring, prevents any organism from producing the maximum number of offspring of which they are physiologically capable. Accordingly, attempts to control certain aspects of these trade-offs, namely the number and timing of offspring, should be seen as integral to human life history and parental investment strategies, regardless of whether these are achieved by physiological or technological means. Indeed, in some cases, a life history perspective provides a more satisfactory explanation than one that assumes that contraceptive uptake reflects only the transmission and adoption of new arbitrary cultural norms. Rather, the initial adoption of contraceptives was a means by which women could regulate their fertility and increase parental investment per child (Alvergne et al. Indeed, 96% of the women adopting contraceptives for the first time had already reproduced: women had nearly four children on average at the point of contraceptive uptake (Alvergne et al. Moreover, those children born before their mothers adopted contraception were less likely to die before the age of five than the children of non-contracepting mothers. It is therefore plausible to argue that the use of contraception can have fitness-enhancing effects, via increased investment in offspring and increased survivorship. Looking at patterns within women, before and after they adopted contraception, it was found that mothers were less likely to 10. This latter result possibly reflects the fact that increases in contraceptive uptake among women also coincided with other developmental initiatives in the region that served to reduce child mortality. Overall, then, women in this sample apparently began using contraception to lengthen the spacing between births, enabling them to invest more in their current children. Moreover, this was a product of individual behavioural innovation by women, rather than by social diffusion of new (arbitrary) cultural norms (ultimately, this must, of course, be the case, given that new norms require a source from which they can diffuse). While shifts in cultural norms of desired family size undoubtedly contribute to fertility decline, it is also possible that, as Alvergne et al. Of course, there are certain situations in which the tight control of fertility clearly does not serve to maximize fitness: voluntarily choosing to remain childless and investing resources in luxury holidays or other consumer goods is one such example (but it is also important to remember that individuals of all species fail to maximize their fitness at times; such variability is, after all, the engine of natural selection). Equally, the demographic transitions that have taken place over the course of the nineteenth and twentieth centuries in Europe and North America, where populations have shifted from high-fertility/high-mortality regimes to low-fertility/low-mortality regimes suggest that people no longer maximize fitness in the industrialized west (Sear et al. These shifts in behaviour have been argued to reflect the adoption of cultural norms, and/or evolved psychological mechanisms aimed at optimizing parental investment in children, which lead to extreme quantity-quality trade-offs in modern industrial settings, neither of which serves to enhance fitness (see the papers in Lawson et al. Even in such apparently clear-cut cases of maladaptive behaviour, some caution is warranted, however. This is because the fecundity and reproductive rates of human females are not constrained by their metabolism as in other mammals, but instead vary with total energy use (Moses and Brown 2003). The relationship between energy use and fertility is not only apparent when cross-species comparisons are made, but also across cultures and across time within human cultures. Indeed, the amount of extrasomatic energy used by a population is a good predictor of fitness components like fertility, child mortality and age at first reproduction (Burger et al. That is, these traits seem to be highly plastic, and respond readily to increases in extrasomatic energy. What this means is that some industrial humans have a much shorter reproductive lifespan than predicted for an ape of our (King Kong) size. That is, the increase in age at first reproduction (which follows from an increase in extrasomatic energy, and hence an effective increase in body size) is not compensated for by a longer period of productivity, as life history theory would predict. Indeed, as Burger and DeLong (2016) point out, there is no genuine theoretically grounded demographic principle for accepting this to be the case; it merely follows from the assumption that sustained economic growth will continue, and returns to human capital will remain high. The application of evolutionary theory to demographic issues provides one very powerful means to understand contemporary shifts in fertility behaviour, and hence to generate more accurate population forecasts. It has proved difficult, however, to identify the mechanism responsible for such effects, and it is equally difficult to predict which women will suffer from them (Burrows et al. We thus need to be aware of the ecological fallacy: relationships at the aggregate level do not necessarily translate to the same relationship at the individual level (see Pollet et al. The study was conducted on a large sample of Finnish women (n = 948), which gave it sufficient statistical power to detect the effect sizes previously reported.

Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog prehypertension in young adults buy exforge 80mg cheap. Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut prehypertension quiz order exforge line. Erythromycin for the prevention and treatment of feeding intolerance in preterm infants blood pressure medication joint pain exforge 80 mg mastercard. Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin pulse pressure with cardiac tamponade order 80mg exforge visa. Use of oral erythromycin for the treatment of gastrointestinal dysmotility in preterm infants blood pressure medication wiki purchase exforge visa. However arrhythmia on ultrasound buy generic exforge 80 mg online, maturation of neuromuscular functions occurs during mid- and late gestation, and this translates to fully functional coordinated gut motility patterns in the full-term healthy neonate capable of independent feeding, ae odigestive protection, and small and large intestinal peristalsis, besides c:yclical regulation of hunger, satiety and feeding. Coordinated movements of gut are crucial for the primary function of the neonatal foregut (to facilitate safe feeding process so as to steer the feedings away from the airway), midgut (gastrointestinal transit of luminal contents to modulate absorption and propulsion), and hindgut (evacuation of excreta to maintain intestinal milieu homeostasis). In this article, we will review and summarize the developmental aspects of (1) pharyngo-esophageal motility, (2) gastrointestinal motility, and (3) colonic motility. Embryologic Aspects of Motility Development the human gut initially arises as a primitive tube from the endoderm of the trilaminar embryo (week 3) and later receives contributions from all the germ cell layers. During week 4, the gut differentiates into three distinct regions (foregut, midgut, and hindgut). The foregut later develops into the airway and lung buds, pharynx, esophagus, stomach, and proximal portion of the duodenum; the midgut gives rise to the remainder of the duodenum, small intestine, and portions of the large intestine up to the distal transverse colon; and the hindgut develops into the distal part of the transverse colon, descending colon, rectum, and proximal part of the anal canal. They colonize the gut through a complex process of migration, proliferation, and differentiation along defined pathways and reach the midgut by week 5 of development and the entire length of the gut by week 7. Interneurons form circuitry chains running both orally and aborally within the myenteric plexus. The orally running interneurons activate excitatory motor neurons, resulting in smooth muscle contraction, and the aborally running interneurons activate inhibitory motor neurons, resulting in smooth muscle relaxation. The excitatory motor neurons release acetylcholine, and the inhibitory motor neurons release nitric oxide or vasoactive intestinal polypeptide. In contrast, sympathetic innervation travels along the mesenteric blood vessels from the prevertebral ganglia and is primarily inhibitory to gut function by decreasing peristalsis and reducing perfusion of the gut. Variations in gut motility and peristaltic patterns occur in prematurely born neonates and are discussed in the latter part of this chapter. When luminal stimulation occurs by mechanoreceptor, chemoreceptor, osmoreceptor, or tension receptor activation, there ensues a cascade of proximal afferent and distal efferent activation. This results in sequential proximal excitatory and distal inhibitory neurotransmission, thus resulting in peristalsis to facilitate gastrointestinal transit. At the level of the esophagus, such sequences also facilitate aerodigestive protection. Pharyngeal swallowing is triggered when a bolus moves from the oral cavity to the pharynx or by direct pharyngeal or esophageal stimulation. An example of spontaneous primary esophageal peristalsis in a premature infant evoked upon pharyngeal contraction, upper esophageal sphincter relaxation, forward propagation of esophageal body peristalsis, and lower esophageal sphincter relaxation. This occurs because of the physical closure of the airway by elevation of the soft palate and larynx, by tilting of the epiglottis, and by the neural suppression of respiration in the brain stem. An example of swallow-independent secondary esophageal peristalsis in a premature infant in response to a mid-esophageal infusion. Absence of pharyngeal waveform, presence of propagating esophageal body peristalsis, upper esophageal sphincter contraction, lower esophageal sphincter relaxation, and complete esophageal propagation are also noted. Such sequences are evoked during esophageal provocations and contribute to esophageal and airway protection by facilitating clearance. These reflexes prevent the ascending spread of the bolus and favor descending propulsion to ensure esophageal clearance. Although the nature and composition of the bolus within the pharyngeal or esophageal lumen can vary, peristalsis remains the single most important function that must occur to favor luminal clearance away from the airway. Similarly, the aerodigestive defense mechanisms during the sleep state also mature with time in preterm infants, as evidenced by the greater ability to remain asleep with less cortical arousal, during esophageal provocation. Many components within each of these levels mature at different times and rates and may explain why infants of similar gestation age demonstrate wide variation in oral feeding skills. The stomach has the lowest frequency of slow waves, occurring at 3 to 5 times/min, whereas it is fastest in the duodenum (9-11 times/min) and then diminishes distally in the midgut (6-8 times/min). Finally, motor function can be modulated by gastrointestinal hormones and peptides, which may exert endocrine, paracrine, or neurocrine activity, resulting in inhibitory. The gastric fundus accommodates the ingested nutrients by receptive relaxation reflex. This is largely mediated by the vagus nerve as stimulation of the mechanoreceptors in the mouth and pharynx and of the distal esophagus induces vago-vagal reflexes that cause relaxation of the gastric reservoir by nitrergic pathways. In contrast to the fundus, the antrum has tonic and phasic activity and is responsible for the churning of nutrients with secretions to initiate early digestion and to empty the stomach contents into the duodenum. Contractile activity in the antrum is coordinated with that in the duodenum to promote emptying of contents into the upper small intestine. Hence, the physical and chemical characteristics of the nutrients entering the duodenum trigger feedback signals to the antrum to hasten or slow emptying. Ultrasonographic studies of the fetal stomach detected gastric emptying occurring as early as 13 weeks of gestation,39 and the length of gastric emptying cycles in fetuses increases just before birth. Quiescence is replaced by persistent motor activity in all four leads shortly after feeding infusion is begun. Neonatal small intestinal motility: motor responses to feeding in term and preterm infants. Peristaltic waves are far spreading and rapid at the proximal small intestine and become shorter and slower toward the distal gut. Full neural integration is inadequate at birth, and gastric emptying and the overall intestinal transit are slower in the preterm infant than in the full-term infant. Overall gut transit can vary from 7 to 14 days and depends on gestational maturation. The small intestine exhibits two basic patterns of motor activity: (1) fed response and (2) fasting response. Fed response facilitates transport of nutrients distally to facilitate digestion and absorption. Although an adult-like fed response is seen in most full-term infants in response to bolus feeding, only about 50% of the preterm infants exhibit such a response. It is usually generated at the duodenum, although it can be generated at any point between the stomach and the ileum. An example of (A) nonmigrating and (B) migrating gastroduodenal motility in a human neonate in the fasting state. Fasting motor activity recorded in the antrum is shown in the top line, activity in the antropyloric junction in the second, and duodenum in the third and fourth. The arrow indicates the presence of migrating motor complex, a phenomenon mediated by motilin, seratoninergic system, or vagal parasympathetic system. Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants. The method of feeding influences motor patterns during fasting as well as feeding. The provision of small early feedings versus no feeding or nonnutritive feedings. Additionally, feeding diluted formula slows the onset and intensity of feeding responses. Phasic contractions appear in the antrum and are temporally coordinated with the occurrence of phasic activity in the three duodenal recording ports. To fulfill these functions, the digesta have to be intensively mixed and slowly moved aborally. There is significant lack of data on colonic motility in human preterm infants, and this is largely the result of technical limitations, need for invasive approaches, and ethical concerns. Colonic motility is quite distinct from small intestinal motility, and regionalization of contractions occurs. The internal anal sphincter, a specialized thickening of circular muscle, maintains a state of tonic contraction, thus maintaining continence in association with the external sphincter. It may be postulated that colonic distention results in neural feedback, inhibiting motor function in the upper intestine. An observation study in preterm infants undergoing routine glycerin enema to stimulate meconium passage was associated with better feeding tolerance,63 but a subsequent randomized trial in preterm infants <32 weeks showed no difference in the time to reach full enteral feeds with daily glycerin suppositories. These reflexes mature in evolution frequency, magnitude, response sensitivity, and associated responses with advanced postnatal maturation. As a consequence, they are more prone to oral feeding difficulties, gastroesophageal reflex, gastric residuals, bowel distention, and delayed meconium passage compared with full-term infants. A combination of local and systemic symptoms and signs needs to be considered together while interpreting the clinical and prognostic significance of nonspecific symptoms and signs of feeding intolerance. However, its safety and efficacy in preterm infants is not completely defined, so use of oral erythromycin should be limited to rescue treatment of severe persistent feeding intolerance. If feeding intolerance limits the ability to provide full feeding volumes to an infant, smaller feeding volumes may be just as capable of inducing maturation. An infant who is intolerant to bolus feedings may tolerate feedings that are given as slow intermittent gavage over 1 hour. Similarly, an infant who has large gastric residuals on a 3-hourly feeding regimen may tolerate feeding better with a short-interval (2-hourly) feeding with smaller feeding volume. Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages. Development of the enteric nervous system, smooth muscle and interstitial cells of Cajal in the human gastrointestinal tract. Heparin-binding epidermal growth factor-like growth factor promotes murine enteric nervous system development and enteric neural crest cell migration. Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders. Analysis of the sacral neural crest cell contribution to the hindgut enteric nervous system in the mouse embryo. Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine. Mechanisms responsible for neuromuscular relaxation in the gastrointestinal tract. Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults. Esophageal body and lower esophageal sphincter function in healthy premature infants. Effect of postnatal maturation on the mechanisms of esophageal propulsion in preterm human neonates: primary and secondary peristalsis. Correlation of esophageal lengths in children with height: application to the Tuttle test without prior esophageal manometry. The relationship between somatic growth and in vivo esophageal segmental and sphincteric growth in human neonates. Esophageal body and upper esophageal sphincter motor responses to esophageal provocation during maturation in preterm newborns. Effect of maturation of the magnitude of mechanosensitive and chemosensitive reflexes in the premature human esophagus. Lower esophageal sphincter relaxation reflex kinetics: effects of peristaltic reflexes and maturation in human premature neonates. Central pattern generation involved in oral and respiratory control for feeding in the term infant. Upper and lower esophageal sphincter kinetics are modified during maturation: effect of pharyngeal stimulus in premature infants. Maturation of upstream and downstream esophageal reflexes in human premature neonates: the role of sleep and awake states. Feeding methods at discharge predict long-term feeding and neurodevelopmental outcomes in preterm infants referred for gastrostomy evaluation. Emergence of oropharyngeal, laryngeal and swallowing activity in the developing fetal upper aerodigestive tract: an ultrasound evaluation. Effect of erythromycin on gastroduodenal contractile activity in developing neonates. Role of endogenous nitric oxide in regulating antropyloroduodenal motility in humans. Gestational and postnatal maturation of duodenal motor responses to intragastric feeding. Enhancement of the non-invasive electroenterogram to identify intestinal pacemaker activity. The migrating motor complex: control mechanisms and its role in health and disease. Clarithromycin treatment in preterm infants: a pilot study for prevention of feeding intolerance. Enteral nutrients promote postnatal maturation of intestinal motor activity in preterm infants. Responses of gastrointestinal peptides and motor activity to milk and water feedings in preterm and term infants. Duodenal motor responses in preterm infants fed formula with varying concentrations and rates of infusion. The intestinal trophic response to enteral food is reduced in parenterally fed preterm pigs and is associated with more nitrergic neurons.

Thinking and doing: the effects of dopamine and oxytocin genes and executive function on mothering behaviours pulse pressure difference buy exforge mastercard. Wasp gene expression supports an evolutionary link between maternal behavior and eusociality heart attack 6 days collections exforge 80mg discount. Brain transcriptomic analysis in paper wasps identifies genes associated with behaviour across social lineages blood pressure 200120 buy line exforge. Timing of intervention affects brain electrical activity in children exposed to severe psychosocial neglect heart attack vs heart failure buy exforge now. Local environment but not genetic differentiation influences biparental care in ten plover populations arteria meningea purchase exforge 80 mg without prescription. Time-contingent change in infanticide and parental behavior induced by ejaculation in male mice arteria ethmoidalis anterior order exforge now. Individual variation in parental care reaction norms: integration of personality and plasticity. Instead, a number of systems are highlighted that have been studied in greater depth, including, for example, what has been learned about the population level effects, both positive and negative, of the intracellular bacterium Wolbachia on the reproductive biology of its insect hosts. I will also highlight several outstanding examples of how endosymbionts, viruses, and various mobile genetic elements can alter host behaviour, often by targeting the nervous system (Moore 2002; Poulin 2011; Lefevre et al. The interactions and behaviour between microbes themselves will also not be covered. This definition is not clear-cut since many mobile genetic elements with bacterial, viral, plasmid, or sometimes even eukaryotic origin become incorporated into the host genome and can make up a large part of it, especially in invertebrates (Drezen et al. While these selfish genetic elements can be suppressed, inactivated, and/or sometimes domesticated to take on a beneficial role for the host organism, they persist because of their selfish vertical transmission. They can also sometimes be found in specialized structures of the gut, although the majority of gut bacteria are free living (Dillon and Dillon 2004). Endosymbionts housed in specific organs or organelles are frequently vertically transmitted from mother to offspring, and hence share part of their evolutionary history with their hosts. This association can lead to cospeciation between hosts and their mutualistic endosymbionts (Moran et al. Some organisms become entirely reliant on their endosymbionts for successful reproduction. Females of the parasitic wasp Asobara tabida are unable to develop ovaries in the absence of their obligate endosymbiotic Wolbachia bacteria (Dedeine et al. For example, some populations of the butterfly Hypolimnas bolina harbour male-killing endosymbionts (Wolbachia) that cause population-level female-biased sex ratios. Variation in male killer prevalence in turn affects female mating behaviour, with females evolving to be less choosy, and male ejaculate size is negatively correlated with the frequency of male killers (Charlat et al. In high-frequency populations, females run the risk of not obtaining sufficient sperm to fertilize all their eggs due to a shortage of males. This sperm shortage is exacerbated by males in these populations suffering ejaculate depletion due to high mating rate, further promoting increased female mating to obtain more sperm (Charlat et al. In African Acraea encedon butterflies, in populations harbouring male-killing endosymbionts, there is even evidence of sex role reversal with females adopting lekking behaviour to advertise their presence to the rare males and thereby increase their mating success (Jiggins et al. In contrast, in populations without male killers, lekking is only performed by males, illustrating the impact of sex ratio distorters in indirectly shaping female mating behaviour. Similarly, sex ratio distorters in flies promote female mating strategies that affect male ejaculate evolution. Some populations of Drosophila pseudoobscura flies harbour a selfish gene (an X-linked meiotic driving chromosome) that kills Y-linked sperm (because they do not pass on the selfish gene) resulting in population-level, female-biased sex ratios (Price et al. Male flies that carry the sperm killer suffer reduced paternity in sperm competition due to low sperm number (Price et al. This in turn favours multiple mating by females as a strategy that effectively biases paternity against sex ratio distorting males. Experiments have shown that females in populations that are at risk of sex ratio distorting males rapidly evolve increased remating frequency to promote sperm competition, demonstrating the potency of sex ratio distorters to alter female mating behaviour (Price et al. As a consequence of increased female remating, male ejaculates evolve in response to the higher risk of sperm competition in these populations (Price et al. This male-female coevolution occurs even when the sex ratio distorter is present at low frequency (5%; Price et al. They achieve this through a variety of sophisticated manipulations by targeting neurological pathways, including neural peptides and neurotransmitters. This is also the case for gut bacteria, and there is growing evidence that gut microbiota can communicate directly with the host nervous system (Cryan and Dinan 2012). Their impacts on behaviour are well documented in vertebrates where specific bacterial neurotransmitters can affect anxiety levels (Forsythe and Kunze 2013), and influence behaviours ranging from cognitive performance to sleep (Cryan and Clark 2016). In insects and arthropods, the brain includes the antennal lobes, that receive input from the olfactory sensory neurons, and mushroom bodies, that play a central role in sensory learning and memory, and microbes have been identified that specifically target these brain regions (Temple and Richard 2015; Strunov et al. In vertebrates, viruses such as rabies, herpes, and measles enter neurons through cell surface receptors, and once inside the neuron, use synapses to spread from cell to cell (Mothes et al. Similarly, the endosymbiont Wolbachia has been recorded in the central nervous system of flies, butterflies, mosquitoes, springtails, and terrestrial isopod hosts (Strunov et al. Gut microbiota can also directly affect the development and function of the nervous system by influencing neurogenesis, neurotransmitter signalling and neurodevelopment and thereby also influence the behaviour of animals (Diaz Heijtz et al. There is even evidence that the host can make use of their endosymbionts to reduce the risk of additional infection. Fungus-growing ants employ a specific behaviour whereby they use antibiotics produced by actinomycetous bacteria housed in specialized structures (infrabuccal pockets) to kill spores of a virulent parasite (Escovopsis) attacking their fungal gardens (Little et al. Many insects, nematodes, and arachnids harbour maternally transmitted endosymbionts, with more than >50% of all insects infected with Wolbachia (Hilgenboecker et al. However, since endosymbionts can only be passed on via females to eggs, the interest of females and the endosymbiont are likely to align over time. Interestingly, this spread in frequency has been accompanied by a shift from parasitic to mutualistic associations with the host. A variety of mutualistic endosymbiotic microbes aid their hosts by providing nutrients or defence against pathogens. Bumblebees and honeybees harbour distinct bacterial communities in their guts that are not shared with related solitary bee species. These microbiota protect bee hosts against a natural trypanosomatid gut parasite, and hence provide an additional benefit of group living to these social insects (Koch and Schmid-Hempel 2011). It has been suggested that one overlooked benefit of group living and sociality is that this serves to facilitate the transmission of beneficial microbes (Lombardo 2008). Microbes that manipulate their hosts to act altruistically in certain situations may be favoured by selection and may therefore also play a role in the evolution of co-operation. Co-operation could favour the microbes as they can be transferred horizontally between hosts during social interactions. Altruistic behaviour could also be favoured by bacteria that are vertically transmitted between mother and offspring, as helping behaviour will increase host survival and reproduction and hence transmission of the microbes (Lewin-Epstein et al. The flip side of social interactions is that they can of course potentially lead to increased risk of disease transmission, and both processes (transmission of pathogenic and protective microbes) are likely to have shaped social behaviour of hosts. Micro-organisms were the first life forms on our planet and therefore have a long history of associating with later emerging multicellular life forms. So it comes as no surprise that microbes have shaped host evolution, and may directly influence the nervous system of their hosts to alter their behaviour (Archie and Tung 2015; Eisthen and Theis 2015). Odour-based signals are 162 8 the Effect of Non-Self Genes on the Behaviour of Hosts also key components in most animal communication. Since these are traits known to shape mate preferences, odour also plays a large role in mate choice. Wolbachia infections are associated with changes in responses to olfactory cues (Peng and Wang 2009; Rohrscheib et al. In Drosophila simulans flies, the wRi strain of Wolbachia increases the responsiveness of flies to food cues, whereas the Wolbachia strains wMel and wMelPop in D. There is a growing realization that microbes can also regulate behaviours between individuals in a social context, and that microbe-based chemical communication commonly occurs between species, as discussed below. Furthermore, these interactions are not restricted to communication between animals. Plants also release volatiles when being consumed by herbivorous insects that in turn can attract parasitoid wasps that attack the herbivores and thereby provide some protection to the plant (Moraes et al. The bacterial pathogen Candidatus modifies the odours released by its citrus tree plant host to attract its vector, the psyllid Diaphorina citri, and thereby facilitate its own proliferation (Martini et al. In humans, the bacterial composition of armpit odours functions as a reliable individual recognition cue as it shows stability over time and conveys distinctive odour profiles (Penn et al. For instance, humans are able to match the scent of monozygotic twins even if they do not live together (Roberts et al. Similar findings have also been shown in a range of mammals where gut microbiota shape the odour cues used in kin recognition (Archie and Tung 2015). There is therefore scope for a complex interaction between diet, the gut microbiota, and resulting individual odours (also see below). In birds, feather-degrading bacteria can affect plumage coloration and therefore influence mate choice. This has been shown in house finches where females prefer redder males that have fewer feather-degrading bacteria than dull males (Shawkey et al. Currently, the precise mechanisms underlying these different results are unclear, but it is possible the former is a case of parasite-mediated sexual selection, with birds of higher quality having lower bacterial loads. In the latter case, brighter males may spend less time preening their feathers and socially dominant males may pay a health cost for dominance, and/or higher bacterial loads are in fact beneficial, but bright birds are better at acquiring these bacteria than their dull male counterparts (Archie and Theis 2011). Internal gut microbiota can also affect odours of animals that directly regulate their sexual behaviours (Sharon et al. Evidence that endosymbionts such as Wolbachia are present in the central nervous system of certain insects and terrestrial isopod hosts suggests that they could act to affect mate preferences (Strunov et al. Intriguingly, in mate choice assays, female mate preferences are dependent on their own Wolbachia variant, with females preferring to mate with males that carry the same compatible Wolbachia strain as themselves. This mate preference disappears after partial depletion of Wolbachia (Miller et al. It is therefore possible that the restriction of Wolbachia to brain areas involved in processing cues relating to sexual behaviour may have evolved to reduce any fitness costs of unrestricted Wolbachia presence in the brain (Strunov et al. The difference in localization of Wolbachia in brain tissue between fly species has been proposed to be the outcome of the age of the association and therefore the potential for coevolution between the host and the endosymbiont. The Wolbachia strain wPau is considered an obligate mutualist that has had a long association with its host and clearing of Wolbachia in D. In other Drosophila species, findings are mixed for the role of Wolbachia-mediated mate preferences. Removal of species-specific Wolbachia infection removes assortative mating preferences. Mating preferences in combination between untreated and treated heterogametic pairs. Grey bars indicate untreated controls; black bars indicate assays with antibiotic-treated flies. However, it is also possible that the different findings could be due to the presence of other agents such as viruses that may also influence mate preferences (Ritschof et al. In the terrestrial isopod Armadillidium vulgare, feminizing Wolbachia influences mate attraction by altering the cuticular compounds and therefore female odours. Males prefer Wolbachia-free females that have different odour profiles, and this preference will result in increased fitness through the production of both sons and daughters (Richard 2017). Sex-specific effects seem likely for maternally inherited endosymbionts that cannot be passed on through males. In mice populations that carry an autosomal segregation distorter (the t-complex), heterozygous females discriminate against heterozygous males using odour cues (Lenington 1991). Females that preferentially mate with males with large eye-stalks enjoy the production of both sons and daughters, and sons in turn enjoy a higher mating success as they will also have large eye-stalks and a mating advantage (Wilkinson et al. Females are just as likely to mate with males whether they carry the sex ratio distorter or not (Price et al. In general, the modest evidence of mate preferences based on selfish genetic elements (Price and Wedell 2008; Wedell 2013) may be due to a lack of linkage between the selfish gene and the female preference gene due to recombination (Nicholls and Butlin 1998). When a virus is transmitted sexually, the host may exhibit increased sexual activity, which can increase virus transmission (Knell and Webberley 2004). Female Helicoverpa zea moths infected with a parasitic virus (Hz-2V) have increased pheromone production and calling frequencies. Virus-infected females are therefore more attractive to males than uninfected females, resulting in increased mating activity and higher reproductive success. This seems to be due to virus-infected females producing six- to sevenfold more pheromone than uninfected females (Burand et al. The Hz-2V virus is both vertically transmitted by infected females to eggs, and horizontally transmitted during mating (Hamm et al. Similarly, Wolbachia infection appears to be associated with differences in male mating activity in flies. This could be a strategy whereby males try to increase their reproductive success by increasing the likelihood of mating with infected and reproductively compatible females, since crosses with uninfected females result in poor offspring production caused by Wolbachia-induced reproductive incompatibility. Mating at higher rates also restores male reproductive compatibility with uninfected females by depleting his Wolbachia-modified sperm (Awrahman et al. This reduction appears to be largely due to reduced effectiveness in courting females, as a higher proportion of initiated courtship attempts are aborted by resistant males.

Cheapest exforge. SEJOY Digital Blood Pressure Cuff.

This bursts the cells and ruptures the nuclear membrane arteria heel generic exforge 80mg mastercard, allowing the chromosomes contained in a nucleus to spill out to form a "chromosome spread heart attack in men order exforge now. Banded chromosomes can be examined using microscopy blood pressure 210 over 110 purchase genuine exforge, and the banded chromosome spreads are often photographed for karyotyping blood pressure chart for age and weight order exforge 80 mg on line. An international symposium in Paris blood pressure medication rebound effect order 80 mg exforge otc, France hypertension 20 year old male buy discount exforge 80mg online, was convened in 1971 to agree on the standard banding pattern for each human chromosome as well as on a standardized nomenclature for identifying chromosome banding patterns based on karyotypes of metaphase chromosomes. This nomenclature remains in use today to ensure accuracy in identifying each chromosome and in describing any chromosome variants or abnormalities. The standardized banding is based on the highly reproducible patterns of some 300 or so lightly and darkly stained bands in chromosomespecific patterns seen on human chromosomes. The banding method is known as G (Giemsa) banding, and it is named after the staining compound called Giemsa stain that is used to generate the chromosome bands. The standardized G-banding nomenclature uses letters and numbers to identify the major and minor band regions of each chromosome. Major regions are subdivided to permit a designation for each light- and dark-band region of a chromosome. Each band is given a designation that specifies the chromosome number, chromosome arm, and band location. Chromosome banding by G banding and other techniques was at one time limited to chromosomes in metaphase. Recently, however, advanced techniques have allowed cytogeneticists to stain chromosomes earlier in the cell cycle. Chromosome banding in prometaphase chromosome spreads produces as many as 2000 chromosome bands. Like the bands seen in metaphase chromosomes, these bands are highly reproducible, and chromosome-specific banding patterns for this phase of the cell cycle are now standardized. Heterochromatic regions are shown as gray and black bands, euchromatic regions as white bands. The patterns and variations observed in chromosome banding are dependent on the various degrees of chromatin condensation. Originally, chromatin condensation was thought to reflect consistent but relatively unimportant regional variation in chromosomes, but there is now clear evidence that chromatin state is directly related to gene transcription. This means that chromosome banding patterns are associated with the distribution of expressed genes. In general, the chromosome regions populated by actively transcribed genes are relatively less condensed than chromosome regions with few transcribed genes, which are more heavily compacted. Regions of lesser chromatin compaction are identified as euchromatin, or as euchromatic regions. Most expressed genes are located in euchromatic regions, where condensation is variable during the cell cycle. Conversely, chromosome regions in which chromatin is tightly condensed are said to contain heterochromatin and are called heterochromatic regions. Heterochromatic regions contain many fewer expressed genes than do euchromatic regions. In G-banded chromosomes, heterochromatin is identified as darkly staining chromosome regions and euchromatin as lightly staining regions. We will return to the theme of chromatin condensation and gene transcription in the last section of this chapter, where we describe the fundamental molecular organization of chromatin and discuss a mutation in Drosophila that demonstrates the role of chromatin condensation in gene transcription. Chromatin and its role in regulating gene transcription is also discussed in Section 13. In the discussion that now follows, we focus on nondisjunction, the failure of chromosomes and sister chromatids to properly disjoin during cell division. As we describe, nondisjunction is the cause of abnormalities of chromosome number in cells. The changes in chromosome number we describe in this section exert their effects primarily by addition or removal of one or more chromosomes of the normal complement in a nucleus. In animal species, but less so in plant species, these abnormalities almost always alter the phenotype, and can have an effect on the development and reduce fertility and viability of the affected organism. Nondisjunction in germ-line cells produces aneuploid gametes-reproductive cells that have one or more extra or missing chromosomes. These gametocytes, contain aneuploid chromosome numbers of n + 1 and n - 1 (assuming only one chromosome pair is affected). If nondisjunction occurs in meiosis I, each of the four resulting gametes are aneuploid-either n + 1 or n - 1. The union of an aneuploid gamete with a normal haploid gamete at fertilization results in a fertilized egg with an aneuploid number of chromosomes that will be either trisomic (2n - 1), having three of one of the chromosomes rather than a homologous pair, or monosomic (2n - 1) having just a single copy of one of the chromosomes rather than a homologous pair. Among the four resulting gametes, two are normal because a normal disjunction took place during each meiotic division. The other two gametes are aneuploid: one contains n + 1 chromosomes and the other n - 1 chromosomes. Trisomic or monosomic fertilized eggs are produced when one of these aneuploid gametes unites with a normal gamete at fertilization. Gene Dosage Alteration In 1913, at about the same time Calvin Bridges was demonstrating the chromosome theory of heredity by examining nondisjunction in fruit flies (see Section 3. Over ensuing decades, this observation was expanded and it was found that aneuploidy profoundly Chromosome Nondisjunction With a few unusual exceptions, the number of chromosomes is the same for males and females of a species, and the number of chromosomes in nuclei of normal cells is a multiple of the haploid number (n), the number in a single set of chromosomes. In nearly all animal species, the total chromosome number is 2n (diploid), but in plants, 3n (triploid) or higher multiples of n are relatively common. Chromosome numbers that are a multiple of the haploid number are identified as euploid. Homologous chromosomes fail to disjoin in meiosis I, and all resulting gametes are aneuploid. Fertilization by a normal haploid gamete produces fertilized eggs that are trisomic (2n + 1) or monosomic (2n - 1). The phenotypic and developmental abnormalities associated with aneuploidy result from changes in gene dosage, the number of copies of a gene in the genome. In a diploid organism, where two copies of a gene, on a homologous pair of chromosomes, generate 100% of gene dosage, a monosomic mutant has just one gene copy and just 50% of normal gene dosage for each gene on the chromosome. In contrast, a trisomic mutant has three copies and 150% of normal gene dosage for each of the genes on the chromosome. Normal fertilization of the resulting gametes generates trisomy, monosomy, or normal diploidy at fertilization. Sophila asks you to ponder these experimental results and to help his colleague by hypothesizing about the likely sequence-binding target of each probe. Review your knowledge of the different portions of chromosomes to which these probes hybridize. Probes longer than about 20 base pairs may hybridize even if there are a few mismatches. Probe C hybridizes to a single location on homologous copies of chromosome 4 that is most likely to be a protein-coding gene. The identity of the gene cannot be determined, however, without additional information. Mastering Genetics Changes in gene dosage lead to an imbalance of gene products from the affected chromosome relative to unaffected chromosomes, and this imbalance is at the heart of alterations of normal development and the production of abnormal phenotypes. Most animals are highly sensitive to changes in gene dosage, and their developmental biology, especially within the nervous system, does not proceed normally in the presence of gene dosage imbalance. In contrast to animals, that are profoundly, often lethally, affected when aneuploidy occurs, gene dosage changes are more easily tolerated in many species of plants, owing in 368 part to their having developmental programs that differ distinctly from those of animals. It is not unusual to find plant strains with more than two copies of each chromosome. Aneuploidy in Humans Humans are enormously sensitive to changes in gene dosage, and almost all human aneuploidies are incompatible with life. Theoretically, there are potentially 24 different kinds of trisomy in humans-one for each autosome, and 10. Yet only autosomal trisomies of chromosomes 13, 18, and 21, and no autosomal monosomies, are seen with any measurable frequency in newborn human infants. Multiple forms of sex-chromosome trisomy are detected with some frequency at birth, however, as is one type of sex-chromosome monosomy (Table 10. A wide variety of other chromosome abnormalities occur in newborn infants as well. Human biologists know that other trisomies and monosomies, not just the ones listed in the table, also occur at conception, but the resulting zygotes almost never survive to be born alive. The explanation for this outcome is that the abnormalities of development that are produced are so severe that either implantation in the uterine wall does not occur, or early zygotic mitotic division is so disrupted that the zygote dies, or fetal development comes to a halt and the fetus spontaneously aborts. The best available data on human reproduction and the rate of aneuploidy comes from studies that monitor women for hormone changes associated with conception and the earliest stages of pregnancy. First, in the first trimester of pregnancy, about half of all human conceptions spontaneously abort, and second, more than half of the spontaneously terminated human pregnancies carry abnormalities of chromosome number or chromosome structure. Other errors producing gametes with abnormal chromosomes add to this level of chromosome error in meiosis. To ascertain the biological basis for the high rate of meiotic nondisjunction in humans, trisomy 21 (Down syndrome)-the most common autosomal trisomy at birth-has been the focus of intense study. Epidemiologic studies conducted over several decades have linked the risk of a child having trisomy 21 to the age of the mother at conception. One theory explaining this association has to do with the fact that meiosis begins in the ovaries of female fetuses. Lindsjo, Down syndrome in live births by single year maternal age interval in a Swedish study: Comparison with results from a New York State study. In the 500,000 or so follicles in each of the two fetal ovaries, meiosis reaches the point of homologous chromosome synapsis in prophase I and then arrests. Meiosis I (homologous chromosome separation) leads to an egg that is released into the fallopian tube. In fact, molecular genetic analysis of the chromosomes in infants with trisomy 21 has indeed determined that more than 90% of cases of trisomy 21 are attributable to a maternal nondisjunction, and that the majority of nondisjunction events are errors in meiosis I. Predominantly, infants with trisomy 21 have two identical copies of a maternal chromosome 21 and one copy of a paternal chromosome 21. Molecular and genomic analyses have also determined that a small number of genes on chromosome 21 are responsible for mental and developmental delays and heart abnormalities, which are the principal symptoms of trisomy 21. Its discovery came from the study of individuals with the symptoms of Down syndrome who have two complete copies of chromosome 21 and an additional fragment of a third copy of the chromosome. This gene also has homologs in mouse and Drosophila, where its protein product participates in the formation of the heart and components of the developing nervous system. A different kind of change in gene dosage is seen in humans with Turner syndrome, a monosomy of the X chromosome in which there is one X chromosome but no second sex chromosome (see Table 10. Despite the occurrence of random X-inactivation in human female embryos that leads to one expressed X chromosome and one inactive X chromosome in each nucleus, two sex chromosomes are necessary for normal early development. Mosaicism Our discussion of random X-inactivation of mammalian females in Chapter 3 identified the phenomenon as an example of naturally occurring mosaicism, in which different cells of the organism contain differently functioning X chromosomes (see Section 3. Mosaicism is the condition of being composed of two or more cell types having different genetic or chromosomal makeup. In addition to the random X-inactivation process, mosaicism can also develop as a consequence of mitotic nondisjunction early in embryogenesis. Mosaicism derived in this way is one of the many kinds of chromosome abnormalities that occur in newborn infants. Union of the gametes described above-with two copies and one copy, respectively, of chromosome 15-results in trisomy 15 in the fertilized egg. By a process known as trisomy rescue, however, some fertilized eggs that are initially trisomic can survive and lead to the formation of a zygote that can survive. In trisomy rescue, one of the extra copies of the chromosome is ejected in one of the first mitotic divisions following fertilization. Thus, one result of trisomy rescue can be a cell with one chromosome from each parent. Alternatively, trisomy rescue could result in a zygote that retains two copies of the chromosome from the same parent, and this is uniparental disomy. Polyploidy is common, particularly in plant species, and can result either from the duplication of full sets of chromosomes or from the combining of chromosome sets from different species. Many types of polyploidy are possible-triploids (3n), tetraploids (4n), pentaploids (5n), hexaploids (6n), octaploids (8n), and so on. Polyploids whose karyotype is comprised of chromosomes derived from a single species are designated autopolyploids (auto =;self<), and polyploids with chromosome sets from two or more species are called allopolyploids (allo =;different<). Mitotic nondisjunction produces one or more aneuploid cell lines that persist and are found in the newborn. Uniparental Disomy A rare abnormality of chromosome content called uniparental disomy has been identified in humans. Uniparental disomy occurs when both copies of a homologous chromosome pair originate from a single parent. The rarer mechanism requires nondisjunction of the same chromosome in both sperm and egg, with the result that a fertilization occurs in which one gamete contributes two copies of the chromosome and the other does not contribute a copy of the chromosome. It involves nondisjunction in one parent that results in an Causes of Autopolyploidy and Allopolyploidy Two mechanisms are most commonly the cause of polyploidy. In these cases, one or both gametes have an extra set of chromosomes that are contributed at fertilization. The second mechanism is mitotic nondisjunction that results in a doubling of chromosome number. The four parental marker alleles are different, so you can expect to see two alleles from one parent and the third allele from the other parent.