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If one allele changes into another from one generation to the next cholesterol levels eyes 10 mg atorvastatin overnight delivery, genotype frequencies can change cholesterol junk food discount 40mg atorvastatin with visa. In natural selection cholesterol test ldl size generic atorvastatin 20 mg free shipping, reproductive success is all-important cholesterol biochemistry definition discount 40mg atorvastatin mastercard, for this is what transmits favorable alleles and weeds out the unfavorable ones, ultimately impacting population structure and therefore microevolution. In the common phrase used synonymously with natural selection-"survival of the fittest"-"fit" actually refers to reproductive success, not to physical prowess or intelligence (unless those traits lead directly to reproductive success). In a Darwinian sense, an unattractive and out-of-shape parent of ten is more "fit" than a gorgeous triathlete with one child. The contribution that mutation makes to counter HardyWeinberg equilibrium is quite small compared to the influence of migration and nonrandom mating, because mutation is rare. The spontaneous mutation rate is only about 30 bases per haploid genome in each gamete. Each of us probably has at least five "lethal equivalents"-alleles or allele combinations that if homozygous would kill us or make us too sick to have children. Retaining a trait is termed positive natural selection, and getting rid of a trait is termed negative natural selection, but the "positive" and "negative" are not value judgments-they merely refer to staying or leaving. Specifically, a sign of positive selection is a gene in humans that has a counterpart in other primates, but in humans has at least one distinctive difference in the amino acid sequence. Heterozygotes and new mutations maintain the frequencies of deleterious alleles in populations. This differential survival to reproduce guided by environmental change is natural selection (figure 15. The chapter opener chronicles natural selection acting on the gene variant that enables people to digest lactose. Inability to digest lactose is actually the wild type condition-it predominated before people began domesticating mammals and drinking their milk. Populations that follow high-starch diets tend to have more copies of the gene that encodes salivary amylase, the digestive enzyme that begins to break down starch in the mouth. Members of populations that follow low-starch diets have fewer copies of the gene-and presumably less of the enzyme. If health conditions impair the ability of individuals of a certain genotype to reproduce, allele frequencies can change. Changing Allele Frequencies © the McGraw-Hill Companies, 2010 295 does not substitute an amino acid does not change the protein, and therefore has no effect on the phenotype. Another sign of positive selection is a gene that varies little, if at all, from person to person. Genes in these regions take part in the sense of smell, digestion, nervous system development, immunity, muscle contraction, and response to stress. Artificial Selection Natural selection acts on preexisting genetic variants and is uncontrolled and largely unpredictable. In contrast, artificial selection is controlled breeding with the intent of perpetuating individuals with a particular phenotype, such as a crop plant or fancy pet. The trait was bred out of the dogs by setting up specific crosses that preserved the coveted spots. The ancestral dog was probably similar to the modern wild dog of Australia, the dingo. Dogs were introduced from southeast Asia in a tiny founder population about 40,000 years ago. People bred the diverse dog breeds of today which, thanks to extreme artificial selection, suffer from more than 300 inherited disorders. Would natural selection have led to the Pekingese with its unstable eyeballs, or the bulldog with its dental woes and notorious dog breath? Interestingly, black wolves and coyotes picked up the mutation that darkens their fur by breeding with domesticated dogs, about 14,000 years ago when canines accompanied people across the Bering Strait land bridge to North America (see figure 16. Dark coat color may have increased in the wolf and coyote populations due to positive selection for better immunity. The trait is the first known example of artificial selection leading to positive selection. Cats were first domesticated in the Near East when agriculture began, about 10,000 years ago. Tuberculosis Ups and Downs-and Ups Natural selection can be seen in the appearance or reemergence of infectious diseases.
Even these features do not entirely isolate germ cells from selfish somatic elements cholesterol medication lipitor side effects purchase atorvastatin with american express. In Drosophila a retrotransposon (412) is very active in the somatic mesoderm that gives rise to the testes and such cells surround and attach to newly arriving primordial germ cells (Brookman et al cholesterol chart for meats purchase cheapest atorvastatin. The suspicion is inescapable that 412 is pumping either copies of itself into the germ cells or other chemicals that aid 412 transposition later in spermatogenesis cholesterol chart webmd discount atorvastatin, but this has not been shown cholesterol medication before blood test order discount atorvastatin online. Direct evidence of a reduced frequency of mutants in the germline comes from studies of mice (Walter et al. Male germline cells have a significantly lower frequency of mutants than somatic tissues (brain, liver, and Sertoli cells, which are somatic cells in the testes;. It is not clear whether this difference is due to a lower mutation rate or fewer cell divisions. Mutant frequencies also differ between germ cells at different stages of development, and between young and old mice. Tests made on purified populations of 8 different spermatogenic cell types show a significantly lower frequency of mutants than do the somatic cells. Moreover, mutant frequencies decline through spermatogenic stages, particularly from type A to type B spermatogonia. Consistent with such selection, there is significant apoptosis at this stage, though the mechanistic basis of the selection is unknown. Mice were genetically engineered to carry a silent lacI gene, and then the gene was recovered from various tissues and introduced into bacteria to measure the frequency of mutations. There was no significant difference among the somatic cell types, but significantly lower mutant frequencies in the seminiferous tubule cells. A, primitive type A spermatogonia; A, type A spermatogonia; B, type B spermatogonia; Pre-L, preleptotene spermatocytes; L + Z, leptotene plus zygotene spermatocytes; Pach. All cell types had a significantly lower mutant frequency than the average somatic frequency. Furthermore, there was a significant decline in mutant frequency between primitive type A spermatogonia and type B spermatogonia. There are no hard data on the matter, and others appear to make the opposite assumption. Whitham and Slobodchikoff (1981) suggest that in trees and other long-lived plants, branches are genetically different, and branches that better fit the local environment. In this way, a single individual may evolve over time and pass on the advantageous changes to its progeny. Indeed, the prerequisites for such evolution have been shown in detail for 2 species of branching red algae, Delisea pulchra and Asparagopsis armata (Monro and Poore 2004). There is significant within-individual phenotypic variation in both species in such fitness-related traits as growth, secondary metabolic concentrations, and rates of tissue loss due to herbivory. Though some aspects of cell lineage selection may be beneficial to the organism and its progeny, we are not aware of any evidence of plants, animals, or any other organism evolving mechanisms to increase the efficacy of cell lineage selection in the germline. If such adaptations are indeed missing (as opposed to merely undiscovered), the implication is that positive selection in the germline is, on average, dangerous and to be avoided. Mutations that are beneficial at the cell lineage level may be more often deleterious than beneficial when passed on in a gamete, or the average effect of those that are deleterious may be larger than the average effect of those that are beneficial. And many transposable elements are active only in the germline and are dormant in somatic cells (see Chap. A more extreme manifestation of the same principle is for a selfish gene to excise itself and be lost from somatic tissues, only to persist in the germline. In all cases our suspicion is that selfish genes must be involved, although in many cases the molecular details are poorly known and in no case is it clear why diminution has evolved. Chromosome diminution was arguably the first selfish genetic phenomenon described, when Boveri observed in 1887 that chromosomes are sharply diminished in size in the somatic cells of Parascaris nematodes (for recent reviews, see Mьller et al. It is noteworthy that chromatin diminution is found in only a few species (7), all of which are parasitic (associated with very high egg number). This contradicts any obvious germline function or function in the first few presomatic cell divisions. It also suggests that there is no net gain, that is, there appears to be no overall reduction in the (somatic) genome in species with genome diminution. In Parascaris univalens the haploid genome consists of 1 compound chromosome with an internal euchromatic segment flanked by large, heterochromatic segments that are discarded from somatic cells. The single large euchromatic section fragments into as many as 50 separate chromosomes.
Three chapters in the story of modern human origins stand out: our beginnings some 200 show cholesterol chart purchase atorvastatin american express,000 years ago; our expansion from Africa; and the populating of the New World cholesterol test units order atorvastatin with mastercard. When might this theoretical "first" woman cholesterol lab values purchase atorvastatin without a prescription, the most recent female ancestor common to us all cholesterol test price philippines buy atorvastatin 5 mg otc, have lived? They concluded that the hypothesized ancestral woman lived about 200,000 years ago, in Africa. About a million people so far have searched for information on their "deep ancestry" by mailing a cheek scraping or saliva sample to any of two dozen companies offering genetic genealogy services. Instead, the goal is to assist people whose searches for the branches of their family trees using conventional documents and memories have left questions. As is the case with direct-to-consumer genetic testing, discussed in chapter 1, ancestry testing websites offer complete and expert information-but people may still request these services with unrealistic expectations. The results are not nearly as specific as what President Barack Obama found when he visited Kenya to meet his half-siblings. Companies are also beginning to offer autosomal markers, tracing parental lines in greater detail. At first companies tested for only four parental populations-African, European, East Asian, and Native American. Geographic regions that a haplogroup may point to may not reflect a particular ethnic or racial group, which are social, not genetic. The project began with studying indigenous peoples, but then expanded Figure 1 the peopling of the planet Humanity arose in East Africa (large red dot) and expanded to the rest of the world. Originated in 7th and 8th centuries when families from north Italy migrated to the Rhine Valley. Modern humans arrived 50,000 years ago; rice farmers from Taiwan came 4,000 years ago and dominate linguistic and archeological evidence. New Findings Unexpected Near East haplogroups found Ashkenazi Jews mt 40% of the 8 million modern Ashkenazim descend from four women Current groups reflect the two religions Lebanon Y Island Southeast Asia (Indonesia, East Malaysia, Philippines) mt From 5,000 to 15,000 years ago, indigenous peoples expanded; Taiwanese farmer contribution was minor such as H. The two species diverged about 5 million years ago, according to extrapolation from fossil and molecular evidence. For this to be so, Africans must have existed longer than other modern peoples, because it takes time for mutations to accumulate. That is, other modern human populations all have at least part of an ancestral African genome, plus mutations that occurred after their ancestors left africa. Expansion Out of Africa the idea of mitochondrial Eve is part of the "out of Africa" view, or replacement hypothesis, of human origins. This may have occurred quickly, in small, isolated pockets, or gradually across a broader swath of the continent. An alternate view, the multiregional hypothesis, has "Eve" 100,000 to "Betty" "Wilma" been largely disproved. It maintained 300,000 years ago that modern humans arose in several places, gradually emerging on a global scale in which people from all over mixed-not the isolated pockets of peoples that the replacement hypothesis envisions. According to the mitochondrial Eve hypothesis, modern neighbors met, and genes flowed from one region to another. In this schematic illustration, the lines represent generations, and the circles, graphic and climatic barriers periodically shrank human populations, females. Human Ancestry © the McGraw-Hill Companies, 2010 while natural selection and genetic drift narrowed the African gene pool. At the same time, new mutations established the haplogroups that are consulted to trace ancestry. Were Neanderthals the only offshoots, known because we happened to find their fossils? Probing genes and genomes for clues to the past is like a photo slowly coming into focus, capturing a portrait of our origins. Populating the New World People spread across Eurasia by 40,000 years ago, as well as elsewhere, and lastly through Siberia (figure 16. From here they could cross the Bering Land Bridge, which emerged between Siberia and Alaska during times when the glaciers had retreated. The land bridge stretched for about 1,000 miles from north to south, emerging as winds from the southwest kept snow away. The areas for several hundred miles on either side of the bridge, and the bridge itself, are called Beringia.
Many X linked recessive disorders are severe or lethal during early life cholesterol in quail eggs buy atorvastatin 10 mg amex, however cholesterol in eggs amount effective atorvastatin 20mg, so that the affected males do not reproduce cholesterol management cheap 40 mg atorvastatin amex. Affected females Occasionally a heterozygous female will show some features of the condition and is referred to as a manifesting carrier cholesterol levels elderly buy atorvastatin 20mg mastercard. This is usually due to non-random X inactivation leading to the chromosome that carries the mutant allele remaining active in most cells. The process of X inactivation that occurs in early embryogenesis is normally random, so that most female carriers would have around 50% of the normal gene remaining active, which is sufficient to prevent clinical signs. Alternatively, X chromosome abnormalities such as Turner syndrome may give rise to X linked disorders in females since, like males, they are hemizygous for genes carried by the X chromosome. The homozygous affected state may occur in females whose father is affected and whose mother is a carrier. This is only likely to occur in common X linked disorders such as red-green colour blindness, or glucose-6-phosphate dehydrogenase deficiency in the Middle East. Genetic assessment is important because of the high recurrence risk and the severity of many X linked disorders. An X linked recessive condition must be considered when the family history indicates maternally related affected males in different generations of the family. Family history is not always positive, however, as new mutations are common, particularly in conditions that are lethal in affected males. Carrier detection is not always straightforward as the mothers of some isolated cases may have normal carrier test results but carry germline mutations leading to a risk of recurrence. In cases where mutation analysis cannot be undertaken, biochemical tests and/or linkage analyses are often possible, but may not give definitive results. Although dominant, females may be less severely affected than males, as in X linked hypophosphataemia (vitamin D-resistant rickets) and oculomotor nystagmus, because of X inactivation which results in expression of the mutant allele in only a proportion of cells. The gene is transmitted through families in the same way as X linked recessive genes: females transmit the mutation to half their sons and half their daughters; males transmit the mutation to all their daughters and none of their sons. The pedigree, however, resembles autosomal dominant inheritance except that there is no male to male transmission and there is an excess of affected females. In some disorders the condition appears to be lethal in affected males, for example focal dermal hypoplasia (Goltz syndrome) and incontinentia pigmenti. In these families there will be fewer males than expected, half of the females will be affected and all surviving males will be unaffected. An affected woman therefore has a one in three chance of having an affected child and two thirds of her children will be girls. Rett syndrome is a disorder that affects girls almost exclusively and usually occurs sporadically, since affected females do not reproduce. This disorder has been shown to be due to a mutation in a gene located at Xq24, confirming that it is an X linked dominant condition. This pattern of inheritance has previously been suggested for such conditions as porcupine skin, hairy ears, and webbed toes. In most conditions in which Y linked inheritance has been postulated the actual mode of inheritance is probably autosomal dominant with sex limitation. Genes involved in male development and spermatogenesis are carried by the Y chromosome, but the mode of inheritance is not demonstrated because of the associated infertility. In 1991 the discovery of unstable trinucleotide repeat expansion mutations identified a novel genetic mechanism underlying a number of important disorders. The number of repeats varies from person to person in the general population, but within the normal range these repeats are stably transmitted. When the number of repeats is increased beyond the normal range, this region becomes unstable with a tendency to increase in size when transmitted to offspring. In some conditions there is a clear distinction between normal and pathological alleles. In others, the expanded alleles may act either as premutations or as full pathological mutations. Premutations do not cause disease but are unstable and likely to expand further when transmitted to offspring. Once the repeat reaches a certain size it becomes a full mutation and disease will occur. Since the age at onset and severity of the disease correlate with the size of the expansion, this phenomenon accounts for the clinical anticipation that is seen in this group of conditions, where age at onset decreases in successive generations of a family. There is a sex bias in the transmission of the most severe forms of some of these disorders, with maternal transmission of congenital myotonic dystrophy and fragile X syndrome, but paternal transmission of juvenile Huntington disease.
Patients with diabetes should be given vaccines to prevent influenza (annual) cholesterol medication no muscle pain purchase atorvastatin 40 mg on-line, pneumococcal disease cholesterol in home grown eggs discount atorvastatin 10 mg line, and hepatitis B cholesterol medication zocor side effects cheap atorvastatin generic. Annually provide an influenza vaccine to all patients with diabetes 6 months of age or older high fiber cholesterol lowering foods discount atorvastatin on line. A one-time revaccination is recommended for individuals 65 years of age or older who were previously immunized when they were younger than 65 years of age if the vaccine was administered more than 5 years ago. Other indications for repeat vaccination include nephrotic syndrome, chronic renal disease, and other immunocompromised states, such as post-organ transplantation. Hepatitis B vaccine (usually 3 doses over 6 months) should be routinely provided to unvaccinated adults with diabetes mellitus ages 18-59 years. The risk of hepatitis B increases twofold for patients with diabetes due primarily to sharing inadequately cleaned blood glucose monitors (including healthcare settings, households, worksite health clinics, schools and camps). Hepatitis B vaccine may be administered to unvaccinated adults with diabetes aged 60 years who are increased risk, including those who live in nursing homes and assisted living facilities and receive blood glucose monitoring. Hepatitis B vaccine is also appropriate pre-dialysis for those with incipient renal failure. Often, the health care provider is unaware of such use, and such interventions may interact with conventional therapy, for example the addition of a glucose-lowering herbal supplement to a sulfonylurea leading to hypoglycemia. The importance of asking individuals which supplements or complementary therapies they use cannot be overemphasized. This information can then lead to a dialogue regarding safety and efficacy issues. A number of traditionally used supplements have shown promise in the treatment of diabetes and are in the process of undergoing large randomized trials. Research studies should continue investigating novel agents for diabetes management. Supplementation with multivitamins and aspirin is generally considered safe; however, megavitamin therapy should be discouraged. Relaxation therapy, yoga, and spiritual healing are helpful to individuals and can be encouraged. Interventions that are potentially harmful or have no real evidence of efficacy clearly should be discouraged. Patients should be commended, however, on their self-determination and encouraged to direct their efforts in areas that have proven benefits. Type 1 diabetes and frequent hypoglycemia or hyperglycemia or HbA1c level greater than glycemic goal. Patients with type 1 diabetes should be managed by a multidisciplinary team using a regimen of 3-4 insulin injections a day in conjunction with 3-4 times/day self-monitoring of blood glucose. Plans for pregnancy Multiple severe complications of diabetes Chronic lack of adherence to their treatment regimen Family problems or significant psychiatric problems interfering with treatment Substantial disability despite adequate therapy Frequent emergency room or hospital admission · · · · · · · Literature Search the literature search for this update began with the results of the literature searches performed in 1995 to develop the guideline and in 2003 for a major update that included literature through February 2003. The literature search conducted in April 2010 for this update used keywords that were similar to those used in previous searches, with the addition of a few new topics for searches. The searches for treatment were performed prospectively on Medline using the major key words of diabetes mellitus; clinical guidelines, controlled trials, cohort studies; adults; and English language; and published from 1/1/2003 to present. Terms for specific topic searches within the major key words included: pre-diabetes or impaired fasting glucose tolerance; glycemic goal; lifestyle modifications: diet, exercise; treatment for type 1 diabetes: insulin; treatment for type 2 diabetes: sulfonylureas, metformin, alpha-glucosidase inhibitors, thiazolidinediones, nonsulfonyluric secretogones (repaglinide, nateglanide), new insulins (glargine, aspart, lispro), exenetide, amylin, liraglutide; sitaglipitin, saxagliptin; screening and treatment for hypertension, lipids, retinopathy, nephropathy, neuropathy, macrovascular disease; and preconception planning in pregnancy. The search was supplemented with very recent controlled trials known to expert members of the panel. Conclusions were based on prospective randomized controlled trials if available, to the exclusion of other data. If randomized controlled trials were not available, observational studies were admitted to consideration. If no such data were available for a given link in the problem formulation, expert opinion was used to estimate effect size. The "strength of recommendation" for key aspects of care was determined by expert opinion. Screening and treatment of hypertension and lipid levels in type 2 diabetes is based on an evidence review and recommendations performed by the American College of Physicians, which included a member of our team. Screening and treatment for retinopathy were based on a literature review performed by the U. While specific measurement details vary (eg, method of data collection, population inclusions and exclusions), the general measures are summarized below. The percentage of patients 1875 years of age who had an HbA1c test within 12 months (measurement period).
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