Christopher M. Rembold, MD
- Professor of Internal Medicine, Department of Medicine, Division
- of Cardiovascular Medicine, University of Virginia, Charlottesville,
- VA, USA
Doctors in Bosnia and Herzegovina have inadequate information treatment resistant schizophrenia generic requip 2mg, knowledge and medical staff to work with intersex babies and their parents medications erectile dysfunction order requip now, and do not have an appropriate multidisciplinary medical team symptoms heart attack purchase cheapest requip and requip. In a few hospitals medicine 219 buy cheapest requip and requip, intersex babies were born medications keppra purchase requip 0.5 mg with mastercard, but no surgery was performed and all intersex babies and children were referred to larger medical centres medicine identifier generic 0.25mg requip amex. This is the first country in the South-East Europe region that has recognized sex characteristics as grounds for discrimination in its anti-discrimination legislation and thus provides protection for intersex people. The gynaecological-obstetric hospital in Tuzla reported six intersex newborns in the last four years. Although this data represent just a fragment of the overall situation, it clearly shows that intersex babies exist and the phenomenon is not that rare. There were cases of intersex children born in hospitals, but no surgical operations were performed. In anti-discrimination law in Bosnia and Herzegovina, sex characteristics are included as grounds for discrimination; however, the implementation of this law is still to be proven. Considerable efforts need to be made to promote acceptance and diversity, through public campaigns and trainings for law enforcement officials. Private health care is also available in the country based on private insurance schemes. The health care system is divided into three levels of care: primary, secondary and tertiary care. In the former Yugoslav Republic of Macedonia, medical specialists in local hospitals are able to diagnose an intersex condition, but they do not perform any medical interventions. They direct parents with an intersex baby or child to the major medical centres where they are treated or, in some cases, further referred to the Institute for Mother and Child in Belgrade, Serbia. The existing medical institutions do not share information about the number of intersex babies and children. There is no multidisciplinary medical team and no internal medical protocols on intersex-related treatment. In an interview,101 a doctor shared information about three cases of intersex teenagers (all of them identified as girls) in her medical practice over a period of more than a decade. All girls had the same symptom (missing periods) when they presented themselves to the gynaecologist. They were referred for further tests and examination by endocrinologists after being diagnosed as intersex. Generally, there is a lack of information about the medical approach to intersex issues in the country. In the former Yugoslav Republic of Macedonia, anti-discrimination law102 identifies gender as grounds for discrimination but not sexual orientation, gender identity or sex characteristics. None of the existing human rights organizations in the former Yugoslav Republic of Macedonia is working on intersex cases. Written internal and follow-up protocols for the treatment of intersex children do not exist. In terms of human rights, legislation and administrative procedures regarding intersex persons are not in place. The following are recommendations to improve the human rights situation and health care for intersex people: 1) Form multidisciplinary medical teams (including currently active specialists) which will be able to establish intersex diagnoses, monitor the condition of intersex infants and children and help parents in the process. In its 2016 Report on Serbia, the European Commission assessment stated that the "legal and institutional framework for the respect of fundamental rights is in place. There is a high level of stigmatization and self-stigmatization of intersex people, particularly in rural areas and there is very little information about intersex people living in Serbia. Study on Homophobia, Transphobia and Discrimination on Grounds of Sexual Orientation and Gender Identity, Legal Report: Serbia, Danish Institute for Human Rights, p. The state-owned health care system is divided into three levels of care: primary, secondary and tertiary care. Treatment for intersex babies and children is available only in medical institutions in the capital, Belgrade. Over a decade, a multidisciplinary team of nine medical specialists have been working with intersex babies and children. Information on existing practices and relevant diagnoses of intersex children were only found in these two institutions. The Ministry of Health and the Statistical Office do not have information about the number of intersex newborns and treated babies in Serbia. Intersex babies and their parents from Bosnia and Herzegovina and the former Yugoslav Republic of Macedonia are in some cases referred to the Institute for Mother and Child in Belgrade based on a personal recommendation by their physician or a peer. The number of intersex cases listed by code of diagnosis per year gives information on the intersex babies that have been treated in Serbia including the babies who are referred from Bosnia and Herzegovina and the former Yugoslav Republic of Macedonia. The Institute for Mother and Child is the leading institution at the national level for infants, and preschool, school-aged and adolescent children. Within the Institute, there is a paediatrics clinic, a paediatric surgical clinic and a centre for science, research and educational activities. There is a multidisciplinary team medical specialists (including four paediatric endocrinologists, three paediatric surgeons, and including a urologist, a geneticist and/or a gynaecologist) that work with intersex babies. Learning from existing practice and treatment of intersex children could be very helpful for other medical practitioners in Serbia and elsewhere in the subregion. When a girl in her later teenage years and her mother were sent to the Institute for Mother and Child with a presumptive diagnosis of being intersex, the paediatric gynaecologist did not refer the girl to the experienced medical team. However, there is no disaggregated list of the number of intersex cases; therefore, there is no public information on that number. The medical protocol contains guidelines for examination, clinical tests, laboratory tests, ultrasound examination, genitography and additional tests for intersex babies. The protocol also contains information on the head doctor, code of procedures, date, place and time. The protocol includes the list of the following procedures: General examination of the newborn: conducted for early detection of an intersex condition. Clinical tests: performed by a neonatologist, paediatric endocrinologist, paediatric surgeon urologist and a gynaecologist and include medical history, paediatric examination and examination of external genitalia. Ultrasound examination of the inner genitals: performed by a radiologist and gynaecologist. Genitography: performed by a radiologist in cooperation with a paediatric gynaecologist and a paediatric surgeon. According to the information received by the staff at the Institute, this happens eight to ten times per year, correlating to the number of intersex babies treated in the Institute. The team also gives written conclusions on the intersex condition of the 110 Interviewed by the author of the study, July 2017. If additional tests 112 are conducted, they provide more insight into the degree of development of external and internal genitalia; the existence, nature and structure of glands; and the reactivity of the external genitalia on androgen hormones. After receiving the results of the additional tests, the multidisciplinary team is called again to establish a diagnosis and recommend treatment for the intersex child. The parents are informed about the possible consequences on the psychosexual development of the child. The medical specialist assists the parents in making a decision on which gender they will raise their child. As stated by the paediatric urologist, 113 psychologists who are sensitized and educated on intersex issues are not included in the team, although there is a necessity for professional psychological support to be provided to the parents in the process of decision-making. Suggested surgical operations are often cosmetic and are not necessary in the opinion of some interviewees. After surgery, some of the children are recommended to take hormones for the rest of their lives and have scars which can cause a lot of pain, especially during childhood. There is no guideline for monitoring the health status of intersex children after the medical and surgical interventions. Sometimes parents do not follow up with scheduled examinations of the baby and the contact with the doctors is lost. It is very important that someone talks with the parents; they are scared and pressured by their families to announce the gender of the child. In this process, we need in our team experienced and sensitized psychologists and counsellors to calm down the parents, help them understand and stop them from making impulsive decisions. Exchange of knowledge and practices among colleagues and other relevant medical co-workers is important. In theory, this can be applied to cases of discrimination against intersex people but no such cases have been recorded as before the court. The Intersex Day of Solidarity and Intersex Awareness Day were announced and celebrated on social networks. Calls for intersex people to join the organization and to establish a support group are open. The organization is established in Belgrade and has working relationships with international intersex organizations. The work focuses on raising awareness, capacity-building and advocating for intersex people and their rights. The Institute for Mother and Child in Belgrade has an experienced multidisciplinary team working with intersex babies and children. Diagnoses related to the intersex condition are collected and stored in the hospital database. Legislation and administrative procedures regarding intersex persons are not in place. The following are recommendwations to improve the human rights situation and health care for intersex people: 1) All medical interventions, tests and medications for the treatment of intersex conditions should be covered by the National Health Insurance. They may have little or no underarm hair, acne or body odor, and they may have pale nipples. If they are not surgically removed, undescended testes have a small chance of becoming cancerous later in life. Partial androgen insensitivity may be quite common, and has been suggested as the cause of infertility in many men whose genitals are of typically male appearance. When the recipe is broken, the adrenal glands, while trying to make cortisone, make an unusually high level of hormones that can cause virilization (masculinization). The Prader scale can be used to measure the degree of virilization of baby genitalia. However, the long-term use of cortisone itself produces significant dependence and other side effects. The syndrome affects roughly 1 in 600 or 700 men, making it one of the most common types of intersex conditions. Males with this syndrome produce insufficient testosterone, leading to late onset of puberty and sometimes failure to complete puberty. Boys develop less muscle mass and have altered bodily distribution of fat and in some cases breast formation. This syndrome may be accompanied by a list of symptoms, including problems with concentration, memory, coordination, fatigue, expression of emotions and social interaction. Testosterone in different forms (gel, injection or capsule) is prescribed to increase energy, to improve concentration, to increase libido, to develop muscle mass and to alter the fat distribution around their body. The syndrome also reduces the risk of osteoporosis and can cause problems with fertility. This syndrome affects girls and women and the development of their ovaries, the production of sex hormones, height and physical sexual maturity. Those affected are almost always short in stature and have different combinations of symptoms including a wide and/or short neck and a low hairline at the back of the neck. Turner syndrome can also cause heart, kidney, thyroid gland and hearing problems; incidence of diabetes; high blood pressure; reduced motor development; and deficiencies in spatial awareness and shortterm memory. Hormone replacement therapy can be used to initiate the period, to develop female secondary sex characteristics and to reduce the risk of low bone density (osteopenia and osteoporosis). A person may have both ovotestis, or they may have a combination of an ovary on one side and a testis or ovotestis on the other. Babies born with ovotestes have "ambiguous genitalia" and some can have labioscrotal fusion and/or hypospadias. If ovarian tissue is at least partially developed, a person can grow breasts and have a period. The urethral opening can be located anywhere along the length of the penis or in the scrotum, and the foreskin is usually split. There are a few types of hypospadias: distal or granular (when the opening is found near the head of the penis), midshaft (when the opening is found in the middle to the lower shaft of the penis), penoscrotal (when the opening is found where the penis and scrotum join) and perineal (when the opening is behind the scrotal sac). If the opening is closer to the scrotum, there is a greater chance of a curved penis. The position and shape of the urethral opening can make it difficult to urinate while standing and/or enable ejaculation. Objective: To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010. Conclusions: the writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization. First Published Online 27 September 2018 common technology with norms stratified by gestational age. Additionally, clinicians should realize that immunoassays lead to more false-positive results. Thus, if laboratory resources do not include liquid chromatographytandem mass spectrometry, a cosyntropin stimulation test should be performed to confirm diagnosis prior to initiation of corticosteroid treatment. Long-term management of patients with congenital adrenal hyperplasia Transition to adult care 6. Restoring functional anatomy by surgery in individuals with congenital adrenal hyperplasia 7. Extensive discussions regarding risks and benefits, shared decision-making, review of potential complications, and fully informed consent need to occur prior to surgery. Mental health practitioners should have specialized expertise in assessing and managing congenital adrenal hyperplasiarelated psychosocial problems.
- Ceroid lipofuscinois, neuronal 4, adult type
- Oculopharyngeal muscular dystrophy
- Buschke Ollendorff syndrome
- Neurocutaneous melanosis
- Nezelof syndrome
- Microphthalmia with limb anomalies
- Spinal muscular atrophy type 1
Acute diarrhea is the most common cause of sodium deficiency medications made from plants order requip no prescription, and oral rehydration depends on the efficient enteric uptake of sodium from isotonic glucose/saline solutions and saves many lives worldwide medicine nobel prize 0.25 mg requip. Vomiting medications metabolized by cyp2d6 discount 2mg requip free shipping, chronic renal disease treatment goals for anxiety purchase requip pills in toronto, renal failure symptoms 4 dpo quality 0.25 mg requip, and chronic respiratory acidosis can result in chloride depletion medications 123 buy cheap requip 0.5 mg line. Toxicity Excessive salt intakes are usually excreted efficiently in healthy individuals, whereas high plasma sodium and chloride are commonly caused by diabetes insipidus, brainstem injury, and dehydration through either excessive sweating or deficient water intake. Excessive salt intake may have roles in the degenerative diseases of coronary heart disease, stroke, gastric cancer, osteoporosis, and bronchial hyperactivity. There are accumulating data from epidemiological studies and controlled clinical trials to indicate an adverse effect of sodium intake on blood pressure, and that most people are sodium sensitive. It now appears that lowering this intermediate or surrogate measure (blood pressure) of disease can be translated into reduced morbidity and mortality of cardiovascular disease from long-term follow-up assessed 1015 years after the original dietary sodium reduction trials. The mechanism linking salt intake with blood pressure is unclear but probably relates to sodium homeostasis. It has been suggested that extracellular sodium concentrations may adversely affect vascular reactivity and growth and stimulate myocordial fibrosis. Low-sodium diets differ in nutrient composition from the prevailing diet, and animal experimentation indicates that low potassium or calcium intake encourages a salt-induced increase in blood pressure, as does feeding simple carbohydrates (sucrose, glucose, or fructose). Copper deficiency in rats has been demonstrated to increase blood pressure independently of sodium intake. Epidemiological and 202 Introduction to Human Nutrition other studies indicate that heavy metals, such as lead and mercury, may also contribute to increased blood pressure. Efficient sodium conservation mechanisms mean that current sodium intakes in many populations are unnecessarily high and are probably much higher than the generally lower sodium diets eaten during the long period of human evolution. Clinical studies indicate that a high-sodium diet increases calcium excretion and measures of bone resorption, thereby suggesting a possible role for high salt intakes in osteoporosis. Cross-cultural epidemiology suggests that high salt intakes are associated with gastric cancer, whereas a low-salt diet is regarded as having a potentially favorable effect in asthma patients. Genetic diseases A number of rare genetic disorders have thrown some light on the pathological mechanisms linking sodium balance and hypertension (pathologically elevated blood pressure). A number of candidate genes have been identified in monogenic forms of low renin saltsensitive hypertension. These encode for enzymes involved in aldosterone biosynthesis or cortisol metabolism and for the epithelial sodium channel. These genetic defects decrease the ability of the renal tubules to excrete sodium. It is possible that similar genetic mechanisms operate in more common forms of hypertension such as essential hypertension and especially salt-sensitive hypertension. Moreover, molecular mechanisms associated with reninangiotensinaldosterone are central to the pathophysiology of this condition. Common essential hypertension, however, is complex and heterogeneous and has a genetic heritability of about 30%. Assessing status the tight regulation of plasma sodium and, in turn, chloride ensures that fluctuations in the plasma concentration of these ions are minimized and changes only occur in certain pathological circumstances. Measurements of plasma sodium, therefore, are of little consequence as far as nutritional status is concerned. Total body (excluding bone) sodium, however, is increased in malnutrition and trauma and this total exchangeable sodium can be measured, with some technical difficulty, using radioisotopes. Salt intakes are notoriously difficult to measure, and urinary sodium excretion is considered to be a valid measure of sodium intake under circumstances where little sodium is lost in sweat. Sodium in urine is easily measured, but the collection of complete 24 h urinary samples is difficult because of subject compliance, and the completeness of these collections should be validated using a marker such as para-amino benzoic acid. Lithium (as carbonate) fused with sodium chloride can act as a reliable tracer to estimate discretionary salt (cooking and table) intakes. Requirements and dietary sources Average requirements for sodium and chloride are estimated to be about 500 and 750 mg/day, respectively. Normal sodium (mostly from salt) intake varies from about 2 g/day to 14 g/day, with chloride (mostly from salt) intakes generally slightly in excess of sodium (Table 9. The amount of discretionary salt added in cooking or at the table appears to vary greatly among individuals and among countries. Discretionary salt intakes can vary from less than 10% to 2030% of total salt intake and these figures emphasize the major effect of processed foods on total salt intakes in most populations (Table 9. Micronutrient interactions the major interactions between sodium (and chloride) and other micronutrients are with respect to potassium and calcium. Data from animals (and some clinical studies) indicate that dietary potassium and calcium potentiate increases in blood pressure in saltsensitive experimental models. There is evidence to suggest that the sodium to potassium ratio correlates more strongly with blood pressure than does either nutrient alone. As indicated previously, the metabolism of sodium, chloride, and potassium is closely related, and sodium and calcium ions have a close metabolic relationship within cells. In contrast to sodium and chloride, nutritional concerns with potassium are mainly concerned with the possibility of underconsumption. Few dietary components affect absorption of potassium, although olive oil can increase and dietary fiber decrease absorption to some extent. The "average" 70 kg man contains about 120 g of potassium, depending on muscle mass, with men having proportionally greater muscle mass, and hence potassium, than women. Potassium is distributed within the body in response to energydependent sodium redistribution. Various hormonal and other factors regulate potassium homeostasis, both within cells and with the external environment. The aldosterone hormone also stimulates potassium excretion by the kidney and, at the same time, conserves sodium. Hypokalemia has opposite effects, such that more potassium is released from cells. Urine is the major excretory route in healthy people, with only small amounts lost in the feces and minimal amounts in sweat. Metabolic function and essentiality Potassium, sodium, and chloride are the major determinants of osmotic pressure and electrolyte balance. Potassium supplementation may have a role to play in treating chronic heart failure, and increased potassium intakes can decrease blood pressure via antagonistic metabolic interactions with sodium, resulting in increased sodium excretion, and also via a direct vasodilatory effect. Oral administration of potassium salts has been shown to improve calcium and phosphorus balance, reduce bone resorption and increase the rate of bone formation. As with potassium depletion, the most important clinical consequence of potassium excess is cardiac arrest. Assessing status the plasma concentration of potassium is not a reliable index of whole-body potassium status. Total body potassium can be measured by 42K dilution or by whole body counting of the naturally abundant 40K to determine the amount of lean body tissue. Requirement and dietary sources Adult requirements for potassium are estimated to be about 2 g/day. Because of potential beneficial antagonistic effects against high salt intakes, higher intakes (around 3. Potassium, like sodium and chloride, is naturally widely distributed in foods (Table 9. Food processing (through leaching) may decrease potassium content as well as increasing salt content. Legumes, nuts, dried fruit, and fresh fruit, especially bananas, melons, avocados, and kiwi fruit, are rich sources of potassium. Major vegetable sources of potassium are potatoes and spinach, although cereal and dairy products, which have a lower potassium content but are consumed in large quantities, are also important dietary sources. People who eat large quantities of fruit and vegetables Reproduced from Sбnchez-Castillo and James in Sadler et al. The physiological importance of potassium in the body covers many systems including cardiovascular, respiratory, digestive, renal, and endocrine. In addition, potassium is a cofactor for enzymes involved in inter alia energy metabolism, glycogenesis, and cellular growth and division. Deficiency symptoms the low concentration of potassium in plasma is tightly regulated. Hypokalemia, however, can result from either excessive uptake of potassium by cells or potassium depletion from the body. Low potassium intakes are unlikely to lead to clinical potassium depletion and hypokalemia except during starvation and anorexia nervosa. The activity of nerves and muscles is affected in potassium depletion, and other clinical sequelae involve cardiac (including cardiac arrest), renal, and Minerals and Trace Elements 205 Table 9. The core of the Earth is thought to be largely composed of iron and it makes up 4. The most common ore is hematite, which is frequently seen as black sands along beaches and streams. Because iron is easy to obtain, its discovery is lost in the history of man, many thousands of years ago. It is therefore paradoxical that although the need for iron was discovered long ago and although it is the most common and cheapest of all metals, iron deficiency is probably the most frequent deficiency disorder in the world and the main remaining nutritional deficiency in Europe. In biological systems, these oxidation states occur primarily as the ferrous (Fe2+) and ferric (Fe3+) forms and these are interchangeable. Absorption, transport, and tissue distribution the iron content of a typical 70 kg adult man is approximately 45 g. The remaining iron is found in body storage as ferritin (20%) and hemosiderin (10%), the two major iron storage proteins. The metabolism of iron differs from that of other minerals in one important respect: there is no physiological mechanism for iron excretion. The body has three unique mechanisms for maintaining iron balance and preventing iron deficiency and iron overload: Reproduced from Sбnchez-Castillo and James in Sadler et al. Micronutrient interactions As might be expected from the close metabolic interactions among the major electrolytes, potassium and sodium dietary interactions may be important in determining the risk of coronary heart disease and stroke. Potassium appears to have positive effects on calcium balance by regulating the acidbase balance and ameliorating any effects of sodium on calcium depletion. It is found in the sun and many types of stars in con- In theory, therefore, when the body needs more iron, absorption is increased, and when the body is iron sufficient, absorption is restricted. This control is not perfect but is still of great importance for the prevention of iron deficiency and excess. Iron from food is 206 Introduction to Human Nutrition absorbed mainly in the duodenum by an active process that transports iron from the gut lumen into the mucosal cell. When required by the body for metabolic processes, iron passes directly through the mucosal cell into the bloodstream, where it is transported by transferrin, together with the iron released from old blood cells (i. If iron is not required by the body, iron in the mucosal cell is stored as ferritin and is excreted in feces when the mucosal cell is exfoliated. Any absorbed iron in excess of needs is stored as ferritin or hemosiderin in the liver, spleen, or bone marrow. Iron can be released from these iron stores for utilization in times of high need, such as during pregnancy. Absorption of iron Plasma: Transferrin iron Spleen: Reticulo-endothelial macrophages Bone marrow: Red blood cell precursors Heme iron is absorbed by a different mechanism from nonheme iron. The heme molecule is absorbed intact into the mucosal cell, where iron is released by the enzyme heme oxygenase. Its absorption is little influenced by the composition of the meal, and varies from 15% to 35% depending on the iron status of the consumer. Although heme iron represents only 10 15% of dietary iron intake in populations with a high meat intake, it could contribute 40% or more of the total absorbed iron (Figure 9. Many poorer regions of the world consume little animal tissue and rely entirely on nonheme iron. The absorption of nonheme iron is strongly influenced by dietary components, which bind iron in the intestinal lumen. The complexes formed can be either insoluble or so tightly bound that the iron is prevented from being absorbed. Under experimental conditions, nonheme iron absorption can vary widely from less than 1% to more than 90%, but under more typical dietary conditions it is usually in the region of 120%. The main inhibitory substances and enhancers of iron absorption are shown in Table 9. Metabolic function and essentiality Iron acts as a catalytic center for a broad spectrum of metabolic functions. As present in hemoglobin, iron is required for the transport of oxygen, critical for cell respiration. Iron is also a component of various tissue enzymes, such as the cytochromes, that are critical for energy production, and enzymes necessary for immune system functioning. There is a main internal loop with a continuous reutilization of iron and an external loop represented by iron losses from the body and absorption from the diet. The importance of iron as an element necessary for life derives from its redox reactivity as it exists in two stable, interchangeable forms, ferrous (Fe2+) and ferric (Fe3+) iron. Deficiency symptoms the progression from adequate iron status to irondeficiency anemia develops in three overlapping stages. The first stage consists of depletion of storage iron, which is characterized by a decrease in serum ferritin, which, in turn, reflects the size of the iron stores in the liver, bone marrow, and spleen. The second stage is a decrease in transported iron and is characterized by a decline in serum iron and an increase in the total iron-binding capacity, as transferrin has more free binding sites than in normal iron status. The third stage develops when the supply of iron is insufficient to provide for enough hemoglobin for new erythrocytes and insufficient to fulfill other physiological functions. During the last stage, free protoporphyrin, destined for hemoglobin, increases in plasma two- to fivefold, indicating a lack of tissue iron. The harmful consequences of iron deficiency occur mainly in conjunction with anemia. Iron deficiency anemia is most common in infants, preschool children, adolescents, and women of child-bearing age, particularly in developing countries. The functional effects of iron deficiency anemia result from both a reduction in circulating hemoglobin and a reduction in iron-containing enzymes and myoglobin.
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The coefficient of the second term is always the same as the power to which the binomial is raised; in our example medicine zolpidem discount 0.25 mg requip otc, this coefficient is 5 and the term is 5p4q symptoms uti buy requip 1mg cheap. For the coefficient of the third term symptoms bronchitis safe requip 2 mg, look back at the preceding term; multiply the coefficient of the preceding term (5 in our example) by the exponent of p in that term (4) and then divide by the number of that term (second term medicine with codeine order requip 2mg without a prescription, or 2) treatment innovations trusted requip 1 mg. So the coefficient of the third term in our example is (5 4)/2 20/2 10 and the term is 10p3q2 treatment zoster ophthalmicus order requip 1mg overnight delivery. Another way to determine the probability of any particular combination of events isn to use the following formula: P= n! The binomial for this situation is (p q)5 because there are five children in the family (n 5). The expansion is: (p q)5 p5 5p4q 10p3q2 10p2q3 5pq4 q5 where P equals the overall probability of event X with probability p occurring s times and event Y with probability q occurring t times. For our albinism example, event X would be the occurrence of a child with albinism (1/4) and event Y would be the occurrence of a child with normal pigmentation (3/4); s would equal the number of children with albi- Basic Principles of Heredity 55 nism (2) and t would equal the number of children with normal pigmentation (3). Applying this formula to obtain the probability of two out of five children having albinism, we obtain: P= = 5! When a testcross is performed, any recessive allele in the unknown genotype is expressed in the progeny, because it will be paired with a recessive allele from the homozygous recessive parent. For example, the recessive allele for yellow eyes in the Oriental fruit fly is represented by ye, whereas the allele for wild-type eye color is represented by ye. At times, the letters for the wild-type allele are dropped and the allele is represented simply by a plus sign. In another way of distinguishing alleles, the first letter is lowercase if the mutant phenotype is recessive and it is uppercase if the mutant phenotype is dominant: for example, narrow leaflet (ln) in soybeans is recessive to broad leaflet (Ln). Superscripts and subscripts are sometimes added to distinguish between genes: Lfr1 and Lfr2 represent dominant mutant alleles at different loci that produce lacerate leaf margins in opium poppies; ElR represents an allele in goats that restricts the length of the ears. For example, the genotype of a goat that is heterozygous for restricted ears might be written El /ElR or simply /ElR. If genotypes at more than one locus are presented together, a space separates the genotypes. For example, a goat heterozygous for a pair of alleles that produces restricted ears and heterozygous for another pair of alleles that produces goiter can be designated by El /ElR G/g. Understanding these ratios and the parental genotypes that produce them will allow you to work simple genetic crosses quickly, without resorting to the Punnett square. Later, we will use these ratios to work more-complicated crosses entailing several loci. A testcross is a cross between an individual with an unknown genotype and one with a homozygous recessive genotype. Lowercase letters are traditionally used to designate recessive alleles, and uppercase letters are for dominant alleles. Two or three letters may be used for a single allele: the recessive allele for heart-shaped leaves in cucumbers is designated hl, and the recessive allele for abnormal sperm-head shape in mice is designated azh. When he crossed the two varieties, the seeds of all the F1 progeny were round and yellow. He then self-fertilized the F1 and obtained the following progeny in the F2: 315 round, yellow seeds; 101 wrinkled, yellow seeds; 108 round, green seeds; and 32 wrinkled, green seeds. Mendel recognized that these traits appeared approximately in a 9: 3: 3: 1 ratio; that is, 9/16 of the progeny were round and yellow, 3/16 were wrinkled and yellow, 3/16 were round and green, and 1/16 were wrinkled and green. This principle states that alleles at different loci separate independently of one another (see Table 3. A common mistake is to think that the principle of segregation and the principle of independent assortment refer to two different processes. The principle of independent assortment is really an extension of the principle of segregation. The principle of segregation states that the two alleles of a locus separate when gametes are formed; the principle of independent assortment states that, when these two alleles separate, their separation is independent of the separation of alleles at other loci. The principle of segregation indicates that the alleles for each locus separate, and one allele for each locus passes to each gamete. Because round is dominant over wrinkled and yellow is dominant over green, the phenotype of the F1 will be round and yellow. When Mendel self-fertilized the F1 plants to produce the F2, the alleles for each locus separated, with one allele going into each gamete. When these four types of gametes are combined to produce the F2 generation, the progeny con- parents are heterozygous for a dominant trait (Aa Aa). The second phenotypic ratio is the 1: 1 ratio, which results from the mating of a homozygous parent and a heterozygous parent. The third phenotypic ratio is not really a ratio: all the offspring have the same phenotype (uniform progeny). If we are interested in the ratios of genotypes instead of phenotypes, there are only three outcomes to remember (Table 3. These simple phenotypic and genotypic ratios and the parental genotypes that produce them provide the key to understanding crosses for a single locus and, as you will see in the next section, for multiple loci. Understanding the nature of these crosses will require an additional principle, the principle of independent assortment. Dihybrid Crosses In addition to his work on monohybrid crosses, Mendel crossed varieties of peas that differed in two characteristics-a dihybrid cross. For example, he had one homozygous variety of pea with seeds that were round and yellow; Basic Principles of Heredity Experiment Question: Do alleles encoding different traits separate independently? Relating the Principle of Independent Assortment to Meiosis An important qualification of the principle of independent assortment is that it applies to characters encoded by loci located on different chromosomes because, like the principle of segregation, it is based wholly on the behavior of chromosomes in meiosis. Each pair of homologous chromosomes separates independently of all other pairs in anaphase I of meiosis (see Figure 2. Genes that happen to be located on the same chromosome will travel together during anaphase I of meiosis and will arrive at the same destination-within the same gamete (unless crossing over takes place). Genes located on the same chromosome therefore do not assort independently (unless they are located sufficiently far apart that crossing over takes place every meiotic division, as will be discussed fully in Chapter 7). Genes located close together on the same chromosome do not, however, assort independently. If we consider only the shape of the seeds, the cross was Rr Rr, which yields a 3: 1 phenotypic ratio (3/4 round and 1 /4 wrinkled progeny, see Table 3. The cross was Yy Yy, which produces a 3: 1 phenotypic ratio (3/4 yellow and 1/4 green progeny). We can now combine these monohybrid ratios by using the multiplication rule to obtain the proportion of progeny with different combinations of seed shape and color. The proportion of progeny with round and yellow seeds is 3/4 3 (the probability of round) /4 (the probability of yel9 low) /16. Rr Yy (a) Expected proportions for first character (shape) Expected proportions for second character (color) Expected proportions for both characters Rr Rr Yy Yy Cross Rr Yy Rr Yy Cross 2. Now follow each branch of the diagram, multiplying the probabilities for each trait along that branch. Another branch leads from round to green, yielding round and green progeny, and so forth. We calculate the probability of progeny with a particular combination of traits by using the multiplication rule: the probability of round (3/4) and yellow (3/4) seeds is 3/4 3/4 9/16. The advantage of the branch diagram is that it helps keep track of all the potential combinations of traits that may appear in the progeny. It can be used to determine phenotypic or genotypic ratios for any number of characteristics. Using probability is much faster than using the Punnett square for crosses that include multiple loci. Genotypic and phenotypic ratios can be quickly worked out by combining, with the multiplication rule, the simple ratios in Tables 3. The probability method is particularly efficient if we need the probability of only a particular phenotype or genotype among the progeny of a cross. Suppose we needed to know the probability of obtaining the genotype Rr yy in the F2 of the dihybrid cross in Figure 3. The probability of obtaining the Rr genotype in a cross of Rr Rr is 1/2 and that of obtaining yy progeny in a cross of Yy Yy is 1/4 (see Table 3. Using the multiplication rule, we find the probability of Rr yy to be 1/2 1/4 1/8. To illustrate the advantage of the probability method, consider the cross Aa Bb cc Dd Ee Aa Bb Cc dd Ee. Suppose we wanted to know the probability of obtaining offspring with the genotype aa bb cc dd ee. If we used a Punnett square to determine this probability, we might be working on the solution for months. However, we can quickly figure the probability of obtaining this one genotype by breaking this cross into a series of single-locus crosses: Progeny cross Aa Aa Bb Bb cc Cc Dd dd Ee Ee Genotype aa bb cc dd ee Probability 1 /4 1 /4 1 /2 1 /2 1 /4 Wrinkled 14 / yy rr yy 14 / Green = 1 16 / Wrinkled, green 14 / 3. Branch diagrams are a convenient way of organizing all the combinations of characteristics (Figure 3. In the first column, list the proportions of the phenotypes for one character (here, 3/4 round and 1/4 wrinkled). In the second column, list the proportions of the phenotypes for the second character (3/4 yellow and 1/4 green) twice, next to each of the phenotypes in the first column: put 3/4 yellow and 1/4 green next to the round phenotype and again next to the wrinkled phenotype. Draw lines between the phenotypes in the first column and each of the phenotypes in the second the probability of an offspring from this cross having genotype aa bb cc dd ee is now easily obtained by using the 1 1 1 1 1 multiplication rule: 1/4 /4 /2 /2 /4 /256. Basic Principles of Heredity 59 Round, yellow Wrinkled, green Worked Problem Not only are the principles of segregation and independent assortment important because they explain how heredity works, but they also provide the means for predicting the outcome of genetic crosses. This predictive power has made genetics a powerful tool in agriculture and other fields, and the ability to apply the principles of heredity is an important skill for all students of genetics. Practice with genetic problems is essential for mastering the basic principles of heredity; no amount of reading and memorization can substitute for the experience gained by deriving solutions to specific problems in genetics. Students may have difficulty with genetics problems when they are unsure of where to begin or how to organize the problem and plan a solution. In genetics, every problem is different, and so no common series of steps can be applied to all genetics problems. Logic and common sense must be used to analyze a problem and arrive at a solution. Nevertheless, certain steps can facilitate the process, and solving the following problem will serve to illustrate these steps. In mice, black coat color (B) is dominant over brown (b), and a solid pattern (S) is dominant over white spotted (s). A homozygous black, spotted mouse is crossed with a homozygous brown, solid mouse. Give the genotypes and phenotypes, along with their expected ratios, of the progeny expected from the testcross. Rr Yy Expected Expected proportions for proportions for first character second character rr yy Expected proportions for both characters Rr rr Cross Yy yy Cross Rr Yy rr yy 12 / 12 / Rr rr 12 / 12 / Yy yy Round Wrinkled Yellow Green 12 / 12 / Yy Rr Yy 12 / 12 = 14 Round, yellow Yellow Rr 12 / Round yy Rr yy 12 / 12 = 14 Round, green Green 12 / Yy rr Yy 12 / 12 = 14 Wrinkled, yellow Yellow 12 / rr 12 / Wrinkled yy rr yy 12 / 12 = 14 Wrinkled, green Green 3. Using the multiplication rule, we find the proportion of round and yellow progeny to be 1 /2 (the probability of round) 1/2 (the probability of yel1 /4. Four combinations of traits with the following low) proportions appear in the offspring: 1/4 Rr Yy, round yellow; 1 /4 Rr yy, round green; 1/4 rr Yy, wrinkled yellow; and 1/4 rr yy, wrinkled green. This problem asks you to provide the genotypes of the parents and the F1, the expected genotypes and phenotypes of the progeny of the testcross, and their expected proportions. This problem provides important information about the dominance relations of the characters and about the mice being crossed. In this problem, symbols are provided for the different alleles (B for black, b for brown, S for solid, and s for spotted); had these symbols not been provided, you would need to choose symbols to represent these alleles. Write down any genetic information that can be determined from the phenotypes alone. The F1 mice are black and solid, both dominant traits, and so the F1 mice must possess at least one black allele (B) and one solid allele (S). At this point, you cannot be certain about the other alleles; so represent the genotype of the F1 as B S, where means that any allele is possible. The brown, spotted mice in the testcross must be bb ss, because both brown and spotted are recessive traits that will be expressed only if two recessive alleles are present. Any cross between a heterozygote and a homozygous recessive genotype produces a 1: 1 phenotypic ratio of progeny (see Table 3. This cross also is between a heterozygote and a homozygous recessive genotype and will produce 1/2 solid (Ss) and 1/2 spotted (ss) progeny (see Table 3. Ss Ў 1 1 ss F1 Testcross Black, solid B S Black, solid B S Brown, spotted bb ss /2 Ss solid /2 ss spotted Finally, determine the proportions of progeny with combinations of these characters by using the branch diagram. After this genotype has been determined, you can predict the results of the testcross and determine the genotypes and phenotypes of the progeny from the testcross. Second, because this cross includes two independently assorting loci, it can be conveniently broken down into two single-locus crosses: one for coat color and the other for spotting. Third, use a branch diagram to determine the proportion of progeny of the testcross with different combinations of the two traits. As a last step, reread the problem, checking to see if your answers are consistent with the information provided. Now that we have stepped through a genetics problem together, try your hand at Problem 30 at the end of the chapter. The ratios of genotypes and phenotypes actually observed among the progeny, however, may deviate from these expectations. For example, in German cockroaches, brown body color (Y) is dominant over yellow body color (y). If we cross a brown, heterozygous cockroach (Yy) with a yellow cockroach (yy), we expect a 1: 1 ratio of brown (Yy) and yellow (yy) progeny. However, the observed numbers might deviate from these expected values; we might in fact see 22 brown and 18 yellow progeny. Chance plays a critical role in genetic crosses, just as it does in flipping a coin. If you flip a coin 1000 times, the proportion of heads and tails obtained will probably be very close to that expected 1: 1 ratio.
Sweet Herb of Paraguay (Stevia). Requip.
- What is Stevia?
- Are there any interactions with medications?
- High blood pressure, diabetes, Preventing pregnancy, heartburn, weight loss, water retention, heart problems, and other conditions.
- Are there safety concerns?
- How does Stevia work?
- Dosing considerations for Stevia.
- What other names is Stevia known by?