{"id":4605,"date":"2019-06-24T13:08:08","date_gmt":"2019-06-24T13:08:08","guid":{"rendered":"https:\/\/pressbooks.ccconline.org\/acchumanbio\/chapter\/5-14-genetic-disorders-3\/"},"modified":"2023-11-30T18:24:10","modified_gmt":"2023-11-30T18:24:10","slug":"5-14-genetic-disorders-3","status":"publish","type":"chapter","link":"https:\/\/pressbooks.ccconline.org\/acchumanbio\/chapter\/5-14-genetic-disorders-3\/","title":{"raw":"5.15\u00a0Genetic Disorders","rendered":"5.15\u00a0Genetic Disorders"},"content":{"raw":" \r\n\r\n[caption id=\"attachment_2561\" align=\"aligncenter\" width=\"564\"]\"Example Figure 5.15.1 Bilateral polydactyly with short fingers in a baby with Ellis-van Creveld syndrome.<\/em>[\/caption]\r\n

Polly Who?<\/h1>\r\nEach hand in the Figure 5.15.1 photo has an extra pinky finger. This is a condition called polydactyly<\/a>, which literally means \"many digits.\" People with polydactyly may have extra fingers and\/or toes, and the condition may affect just one hand or foot, or both hands and feet. Polydactyly is often genetic in origin and may be part of a genetic disorder associated with other abnormalities.\r\n
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What Are Genetic Disorders?<\/h1>\r\n<\/div>\r\n[pb_glossary id=\"2562\"]Genetic disorders[\/pb_glossary]<\/strong>\u00a0are diseases, syndromes, or other abnormal conditions caused by\u00a0[pb_glossary id=\"2381\"]mutations[\/pb_glossary]\u00a0in one or more genes, or by chromosomal alterations. Genetic disorders are typically present at birth, but they should not be confused with\u00a0[pb_glossary id=\"2563\"]congenital disorders[\/pb_glossary]<\/strong>,\u00a0a category that includes\u00a0any disorder present at birth, regardless of cause. Some congenital disorders are not caused by genetic mutations or chromosomal alterations. Instead, they are caused by problems that arise during embryonic or fetal\u00a0development, or during the process of birth. An example of a nongenetic congenital disorder is fetal alcohol syndrome<\/a>. This is a collection of birth defects, including facial anomalies and intellectual disability, caused by maternal alcohol consumption during\u00a0pregnancy.\r\n
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Genetic Disorders Caused by Mutations<\/h1>\r\n<\/div>\r\nTable 5.15.1 lists several genetic disorders caused by mutations in just one gene. Some of the disorders are caused by mutations in autosomal genes, others by mutations in X-linked genes. Which disorders would you expect to be more common in males than females?\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Table 5.15.1: Types of Genetic Disorders, Their Effects and Mode of Inheritance<\/caption>\r\n
Genetic Disorder<\/th>\r\nDirect Effect of\u00a0Mutation<\/th>\r\nSigns and Symptoms of the Disorder<\/th>\r\nMode of Inheritance<\/th>\r\n<\/tr>\r\n
Marfan syndrome<\/a><\/td>\r\nDefective protein in connective tissue<\/td>\r\nHeart and bone defects and unusually long, slender limbs and fingers<\/td>\r\nAutosomal dominant<\/td>\r\n<\/tr>\r\n
Sickle cell anemia<\/a><\/td>\r\nAbnormal hemoglobin protein in red blood cells<\/td>\r\nSickle-shaped red blood cells that clog tiny blood vessels, causing pain and damaging organs and joints<\/td>\r\nAutosomal recessive<\/td>\r\n<\/tr>\r\n
Hypophosphatemic\u00a0 (Vitamin D-resistant) rickets<\/a><\/td>\r\nLack of a substance needed for bones to absorb minerals<\/td>\r\nSoft bones that easily become deformed, leading to bowed legs and other skeletal deformities<\/td>\r\nX-linked dominant<\/td>\r\n<\/tr>\r\n
Hemophilia<\/a> A<\/td>\r\nReduced activity of a protein needed for blood clotting<\/td>\r\nInternal and external bleeding that occurs easily and is difficult to control<\/td>\r\nX-linked recessive<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\nVery few genetic disorders are controlled by [pb_glossary id=\"5973\"]dominant[\/pb_glossary] mutant\u00a0[pHypophosphatemicb_glossary id=\"2119\"]alleles[\/pb_glossary]. A dominant allele is expressed in every individual who inherits even one copy of it. If it causes a serious disorder, affected people may die young and fail to reproduce. Therefore, the mutant dominant allele is likely to die out of a\u00a0population.\r\n\r\nA recessive mutant allele \u2014 such as the allele that causes sickle cell anemia<\/a> or cystic fibrosis<\/a> \u2014 is not expressed in people who inherit just\u00a0one <\/em>copy of it. These people are called\u00a0[pb_glossary id=\"2564\"]carriers[\/pb_glossary]<\/strong>. They do not have the disorder themselves, but they carry the mutant allele and their offspring can inherit it. Thus, the allele is likely to pass on to the next generation, rather than die out.\r\n
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Genetic Disorders Caused by Chromosomal Alterations<\/h1>\r\n<\/div>\r\nMistakes may occur during\u00a0[pb_glossary id=\"2486\"]meiosis[\/pb_glossary]\u00a0that result in\u00a0[pb_glossary id=\"2565\"]nondisjunction[\/pb_glossary]<\/strong>. This is the failure of replicated\u00a0[pb_glossary id=\"5619\"]chromosomes[\/pb_glossary]\u00a0to separate properly during\u00a0meiosis. Some of the resulting [pb_glossary id=\"6023\"]gametes[\/pb_glossary] will be missing all or part of a chromosome, while others will have an extra copy of all or part of the chromosome. If such gametes are fertilized and form [pb_glossary id=\"2471\"]zygotes[\/pb_glossary], they usually do not survive. If they do survive, the individuals are likely to have serious genetic disorders.\r\n\r\nTable 5.15.2 lists several genetic disorders that are caused by abnormal numbers of chromosomes. Most chromosomal disorders involve the X chromosome. The X and Y chromosomes are the only chromosome pair in which the two chromosomes are very different in size. This explains why nondisjunction tends to occur more frequently in sex chromosomes than in autosomes.\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Table 5.15.2: Genetic Disorders, Their Genotypes, and Phenotypic Effects<\/caption>\r\n
Genetic Disorder<\/th>\r\nGenotype<\/th>\r\nPhenotypic Effects<\/th>\r\n<\/tr>\r\n<\/thead>\r\n
Down syndrome<\/a><\/td>\r\nExtra copy (complete or partial) of chromosome 21 (see Figure 5.15.3)<\/td>\r\nDevelopmental delays, distinctive facial appearance, and other abnormalities (see Figure 5.15.2)<\/td>\r\n<\/tr>\r\n
Turner syndrome<\/a><\/td>\r\nOne X chromosome but no other sex chromosome (XO)<\/td>\r\nFemale with short height and infertility(inability to reproduce)<\/td>\r\n<\/tr>\r\n
Triple X syndrome<\/a><\/td>\r\nThree X chromosomes (XXX)<\/td>\r\nFemale with mild developmental delays and menstrual irregularities<\/td>\r\n<\/tr>\r\n
Klinefelter syndrome<\/a><\/td>\r\nOne Y chromosome and two or more X chromosomes (XXY, XXXY)<\/td>\r\nMale with problems in sexual development and reduced levels of the male hormone testosterone<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n\r\n\r\n\r\n\r\n
\r\n\r\n[caption id=\"attachment_2567\" align=\"alignnone\" width=\"638\"]\"Image Figure 5.15.2 Family with down syndrome child.<\/em>[\/caption]<\/td>\r\n\r\n\r\n[caption id=\"attachment_2566\" align=\"alignnone\" width=\"407\"]\"Down Figure 5.15.3 Trisomy 21 (Down Syndrome) Karyotype.<\/em>[\/caption]<\/td>\r\n<\/tr>\r\n
<\/td>\r\n<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\nA karyotype is a picture of a cell's chromosomes. In Figure 5.15.3, note the extra chromosome 21. In Figure 5.15.2, a young man with Down syndrome exhibits the characteristic facial appearance.<\/span>\r\n

Diagnosing and Treating Genetic Disorders<\/h1>\r\nA genetic disorder that is caused by a\u00a0mutation\u00a0can be inherited. Therefore, people with a genetic disorder in their family may be concerned about having children with the disorder. A genetic counselor can help them understand the risks of their children being affected. If they decide to have children, they may be advised to have prenatal (\u201cbefore birth\u201d) testing to see if the fetus has any genetic abnormalities. One method of prenatal testing is [pb_glossary id=\"2570\"]amniocentesis[\/pb_glossary]. In this procedure, a few fetal\u00a0cells\u00a0are extracted from the fluid surrounding the fetus\u00a0in utero<\/em>, and the fetal chromosomes are examined. Down syndrome and other chromosomal alterations can be detected in this way.\r\n\r\n[caption id=\"attachment_2571\" align=\"alignleft\" width=\"412\"]\"Image Figure 5.15.3 The PKU test is conducted shortly after birth in order to determine if an infant has higher than normal levels of phenylalanine.<\/em>[\/caption]\r\n\r\nThe symptoms of genetic disorders can sometimes be treated or prevented. In the genetic disorder called phenylketonuria<\/a> (PKU), for example, the amino acid phenylalanine builds up in the body to harmful levels. PKU is caused by a [pb_glossary id=\"2381\"]mutation[\/pb_glossary] in a gene that normally codes for an [pb_glossary id=\"5757\"]enzyme[\/pb_glossary] needed to break down phenylalanine. When a person with PKU consumes foods high in phenylalanine (including many high-protein foods), the buildup of PKU can lead to serious health problems. In infants and young children, the build-up of phenylalanine can cause intellectual disability and delayed development, along with other serious problems. All babies in Canada and the United States and many other countries are screened for PKU soon after birth.\u00a0 As shown in Figure 5.15.3, the PKU test involves collecting a small amount of blood from the infant, typically from the heel using a small lancet.\u00a0 The blood is collected on a special type of filter paper and then brought to a laboratory for analysis. If PKU is diagnosed, the infant can be fed a low-phenylalanine diet, which prevents the buildup of phenylalanine and the health problems associated with it, including intellectual disability. As long as a low-phenylalanine diet is followed throughout life, most symptoms of the disorder can be prevented.\r\n
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Curing Genetic Disorders<\/h1>\r\n<\/div>\r\nCures for genetic disorders are still in the early stages of development. One potential cure is\u00a0gene therapy.\u00a0[pb_glossary id=\"2573\"]Gene therapy[\/pb_glossary]<\/strong>\u00a0is an experimental technique that uses genes to treat or prevent disease. In gene therapy, normal [pb_glossary id=\"5521\"]genes[\/pb_glossary] are introduced into [pb_glossary id=\"5665\"]cells[\/pb_glossary] to compensate for abnormal genes. If a mutated gene causes a necessary [pb_glossary id=\"5813\"]protein[\/pb_glossary] to be nonfunctional or missing, gene therapy may be able to introduce a normal copy of the gene to produce the needed functional protein.\r\n\r\nA gene inserted directly into a cell usually does not function, so a carrier called a\u00a0[pb_glossary id=\"2574\"]vector<\/strong> [\/pb_glossary]is genetically engineered to deliver the gene (see Figure 5.15.<\/em>4<\/em> illustration). Certain viruses, such as adenoviruses, are often used as vectors. They can deliver the new gene by infecting cells. The viruses are modified so they do not cause disease when used in people. If the treatment is successful, the new gene delivered by the vector will allow the synthesis of a functioning protein. Researchers still must overcome many technical challenges before gene therapy will be a practical approach to curing genetic disorders.<\/span>\r\n\r\n \r\n\r\n[caption id=\"attachment_2575\" align=\"aligncenter\" width=\"559\"]\"Image Figure 5.15.4 Gene therapy is an experimental technique for curing a genetic disorder by changing the patient's genetic makeup. Typically, gene therapy involves introducing a normal copy of a mutant gene into the patient's cells.<\/em>[\/caption]\r\n\r\n
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Feature: Human Biology in the News<\/h1>\r\n<\/div>\r\n\r\n[caption id=\"attachment_2568\" align=\"alignright\" width=\"377\"]\"Image Figure 5.15.5 A Boy With Down Syndrome.<\/em>[\/caption]\r\n\r\nDown syndrome is the most common genetic cause of intellectual disability. It occurs in about one in every 700 live births, and it currently affects nearly half a million Americans. Until recently, scientists thought that the changes leading to intellectual disability in people with Down syndrome all happen before birth.\r\n\r\nEven more recently, researchers discovered a genetic abnormality that affects brain development in people with Down syndrome throughout\u00a0childhood\u00a0and into\u00a0adulthood. The newly discovered genetic abnormality changes\u00a0communication\u00a0between nerve cells in the brain, resulting in slower transmission of\u00a0nerve impulses. This finding may eventually allow the development of strategies to promote brain functioning in Down syndrome patients, and it may also be applicable to other development disabilities, such as autism. The results of this promising study were published in the March 16, 2016 issue of the scientific journal\u00a0Neuron.<\/em>\r\n
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5.15 Summary<\/span><\/h1>\r\n<\/header>\r\n
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