第五组血友病问题讨论

1、组序列的重组会造成哪些其他疾病？请比较血友病重组机制与Smith-Magenis 综性高胆固醇血症的异同。重复的合征和脊髓肌肉性肌萎缩（KENNEDY 病）（CAG）n 重复病（CAG）n 序列重复脆性 X 综合征（CGG）n 重复强直性肌营养不良（CTG）n 重复同源重组（Homologous Recombination) :是指发生在非姐妹染色单体（sister chromatin) 之间或同一上含有同源序列的 DNA之间或之内的重新组合。同源重组需要一系列的蛋白质催化。同源重组反应通常根据交叉或 Holliday 结构（Holliday JunctureStructure) 的形成和拆分

2、分为三个阶段，即前联会体阶段、联会体形成和 Holliday 结构的拆分。异常重组：完全不依赖于序列间的同源性而使一段 DNA 序列另一段中，但在形成重组时往往是依赖于 DNA而完成重组过程。eg.转座作用,需要转座酶和对转座区域DNA 的。位点专一性重组: 这类重组在原核生物中最为典型。这种重组依赖小范围的同源序列的联会，重组也只限于在这一小范围内，其重组也只涉及特置的短同源区或是特定点碱基序列之间。重组时发确的切割，连接反应，DNA 不失去不。俩个 DNA并不交换对等的部分，有时是一个 DNA称为整合式重组。整合到另一个 DNA中，因此将这种重组又同源重组的两个模型：1.Holiday模型

3、：2. Meselson-Radding 模型重 组机制血友病X 连锁隐性遗传内重组Cpg 核苷酸突变都遵循孟德尔遗传 规律性高胆固醇血症常显性遗传性疾病17.18 号外显子单个碱基突变13 外显子 15 内含子 Alu 序列却 5.0KbSmith-Magenis综合征从17 号的特定区域缺失的遗传物质17 号的内含子/碱基的What is Smith-Magenis syndrome?Smith-Magenis syndrome is a developmental disorder that affects many parts of the body. The major featur

4、es of this condition include mild to moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems.Most people with Smith-Magenis syndrome have a broad, square-shaped face with deep-set eyes, full cheeks, and a prominen

5、t lower jaw. The middle of the face and the bridge of the nose often appear flattened. The mouth tends to turn downward with a full, outward-curving upper lip. These facial differences can be subtle in early childhood, but they usually become more distinctive in later childhood and adulthood. Dental

6、 abnormalities are also common in affected individuals.Disrupted sleep patterns are characteristic of Smith-Magenis syndrome, typically beginningearly in life. Affected people may be very sleepy during the day, but they have trouble falling asleep and awaken several times each night.People with Smit

7、h-Magenis syndrome have affectionate, engagingalities, but mostalso have behavioral problems. These include frequent temper tantrums and outbursts, aggression, anxiety, impulsiveness, and difficulty paying attention. Self-injury, including biting, hitting, head banging, and skin picking, is very com

8、mon. Repetitive self-hugging is a behavioral trait that may be unique to Smith-Magenis syndrome. People with this condition also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip").Other signs and symptoms of Smith-Magenis syndrome in

9、clude short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia) and

10、other vision problems. Although less common, heart and kidney defects also have been reported in people with Smith-Magenis syndrome.How common is Smith-Magenis syndrome?Smith-Magenis syndrome affects at least 1 in 25,000 individuals worldwide. Researchers believe that many people with this condition

11、 are not diagnosed, however, so the true prevalence may be closer to 1 in 15,000 individuals.What are tetic changes related to Smith-Magenis syndrome?Most people with Smith-Magenis syndrome have a deletion of genetic material from a specific region of chromosome 17. Although this region contains mul

12、tiple genes, researchers believe that the loss of one particular gene, RAI1, in each cell is responsible for most of the characteristic features of this condition. The loss of other genes in the deleted region may help explain why the features of Smith-Magenis syndrome vary among affected individual

13、s. A small percentage of people with Smith-Magenis syndrome have a mutation in the RAI1 gene instead of a chromosomal deletion. Although these individuals have many of the major features of the condition, they are less likely than people with a chromosomal deletion to have short stature, hearing los

14、s, and heart or kidney abnormalities.The RAI1 gene provides instructions for making a protein whose function is unknown.Mutations in one copy of this gene lead to the production of a nonfunctional version of the RAI1 protein or reduce the amount of this protein that is produced in cells. Researchers

15、 are uncertain how changes in this protein result in the physical, mental, and behavioral problems associated with Smith-Magenis syndrome.Read more about the RAI1 gene and chromosome 17. Can Smith-Magenis syndrome be inherited?Smith-Magenis syndrome is typically not inherited. This condition usually

16、 results from agenetic change that occurs during the formation of reproductive cells (eggs or sperm) or inearly fdevelopment. Most often, people with Smith-Magenis syndrome have no historyof the condition in their family.Where can I find information about diagnosis or management of Smith-Magenis syn

17、drome? These resources address the diagnosis or management of Smith-Magenis syndrome and may include treatment providers.Gene Review: Smith-Magenis SyndromeThis link leads to a site outside Genetics Home Reference.Genetic Testing Registry: Smith-Magenis syndromeThis link leads to a site outside Gene

18、tics Home Reference.MedlinePlus Encyclopedia: Intellectual DisabilityThis link leads to a site outside Genetics Home Reference.You might also find information on the diagnosis or management of Smith-Magenis syndrome in Educational resources and Patient support.General information about the diagnosis

19、 and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.Where can I find addition

20、al information about Smith-Magenis syndrome?You may find the following resources about Smith-Magenis syndrome helpful. Thesematerials are written for teral public.MedlinePlus - Health information (3 links)Genetic and Rare Diseases Information CenterThis link leads to a site outside Genetics Home Ref

21、erence. - Information about genetic conditions and rare diseasesEducational resources - Information pages (4 links) Patient support - For patients and families (4 links)You may also be interested in these resources, which are designed for healthcare professionals and researchers.Gene ReviewsThis lin

22、k leads to a site outside Genetics Home Reference. - Clinical summary Genetic Testing Registry - Repository of genetic test information (1 link) ClinicalTThis link leads to a site outside Genetics Home Reference. - Linking patients to medical researchPubMedThis link leads to a site outside

23、Genetics Home Reference. - Recent literature OMIMThis link leads to a site outside Genetics Home Reference. - Genetic disorder catalog What other names do people use for Smith-Magenis syndrome?17p11.2 monosomy17p- syndromechromosome 17p deletion syndrome deletion 17p syndromepartial monosomy 17p SMS

24、For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.What if I still have specific questions about Smith-Magenis syndrome?Ask the Genetic and Rare Diseases Information CenterT

25、his link leads to a site outside Genetics Home Reference.Where can I find general information about genetic conditions?The Handbook provides basic information about genetics in clear language. What does it mean if a disorder seems to run in my family?What is a chromosome?Can changes in the number of

26、 chromosomes affect health and development? Are chromosomal disorders inherited?These links provide additional genetics resources that may be useful. Genetics and HealthResources for Patients and FamiliesResources for Health ProfessionalsWhat glossary definitions help with understandinith-Magenis sy

27、ndrome?anxiety ; cell ; chromosome ; contiguous ; contiguous gene deletion syndrome ; deletion ; disability ; gene ; gene deletion ; inherited ; injury ; kidney ; lower jaw ; monosomy ; mutation ; myopia ; nearsightedness ; prevalence ; protein ; reproductive cells ; scoliosis ;sensitivity ; short s

28、tature ; sperm ; stature ; syndrome ; traitYou may find definitions for these and many other terms in t Glossary.See also Understanding Medical Terminology.References (9 links)etics Home ReferenceThe resources on this site should not be used as a substitute for professional medical care oradvice. Us

29、ers seeking information about aal genetic disease, syndrome, or conditionshould consult with a qualified healthcare professional. See How can I find a geneticsprofessional in my area? in the Handbook.What is hypercholesterolemia?Hypercholesterolemia is a condition characterized by very high levels o

30、f cholesterol in the blood. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). The body needs this substance to build cell membranes, make certain hormones,and produc

31、e compounds that aid in fat digestion. Too much cholesterol, however, increases a 's risk of developing heart disease.People with hypercholesterolemia have a high risk of developing a form of heart disease called coronary artery disease. This condition occurs when excess cholesterol in the blood

32、stream is deposited in the walls of blood vessels, particularly in the arteries that supply blood to the heart (coronary arteries). The abnormal buildup of cholesterol forms clumps (plaque) that narrow and harden artery walls. As the clumps get bigger, they can clog thearteries and restrict the flow

33、 of blood to the heart. The buildup of plaque in coronaryarteries causes a form of chest pain called angina and greatly increases ahaving a heart attack.'s risk ofInherited forms of hypercholesterolemia can also cause health problems related to the buildup of excess cholesterol in other tissues.

34、 If cholesterol accumulates in tendons, it causes characteristic growths called tendon xanthomas. These growths most often affect the Achilles tendons and tendons in the hands and fingers. Yellowish cholesterol deposits under the skin of the eyelids are known as xanthelasmata. Cholesterol can also a

35、ccumulate at the edges of the clear, front surface of the eye (the cornea), leading to a gray-colored ring called an arcus cornealis.How common is hypercholesterolemia?More than 34 million American adults have elevated blood cholesterol levels (higher than 240 mg/dL). Inherited forms of hypercholest

36、erolemia, which cause even higher levels of cholesterol, occur less frequently. The most common inherited form of high cholesterol is called familial hypercholesterolemia. This condition affects about 1 in 500 people in most countries. Familial hypercholesterolemia occurs more frequently in certain

37、populations, including Afrikaners in South Africa, French Canadians, Lebanese, and Finns.What genes are related to hypercholesterolemia?Mutations in the APOB, LDLR, LDLRAP1, and PCSK9 genes cause hypercholesterolemia. High blood cholesterol levels typically result from a combination of genetic and e

38、nvironmental risk factors. Lifestyle choices including diet, exercise, and tobacco smoking strongly influence the amount of cholesterol in the blood. Additional factors that impactcholesterol levels include aobesity. A small percentage of's gender, age, and health problems such as diabetes andal

39、l people with high cholesterol have an inherited form ofhypercholesterolemia. The most common cause of inherited high cholesterol is a condition known as familial hypercholesterolemia, which results from mutations in the LDLR gene.The LDLR gene provides instructions for making a protein called a low

40、-density lipoprotein receptor. This type of receptor binds to particles called low-density lipoproteins (LDLs), which are the primary carriers of cholesterol in the blood. By removing low-density lipoproteins from the bloodstream, these receptors play a critical role in regulating cholesterol levels

41、. Some LDLR mutations reduce the number of low-density lipoprotein receptors produced within cells. Other mutations disrupt the receptors' ability to remove low-density lipoproteins from the bloodstream. As a result, people with mutations in the LDLR gene have very high levels of blood cholester

42、ol. As the excess cholesterol circulates through the bloodstream, it is deposited abnormally in tissues such as the skin, tendons, and arteries that supply blood to the heart.Less commonly, hypercholesterolemia can be caused by mutations in the APOB, LDLRAP1,or PCSK9 gene. Changes in the APOB gene r

43、esult in a form of inherited hypercholesterolemia known as familial defective apolipoprotein B-100 (FDB). LDLRAP1 mutations are responsible for another type of inherited high cholesterol, autosomal recessive hypercholesterolemia (ARH). Proteins produced from the APOB, LDLRAP1, and PCSK9 genes are es

44、sential for the normal function of low-density lipoprotein receptors. Mutations in any of these genes prevent the cell from making functional receptors or alter the receptors' function. Hypercholesterolemia results when low-density lipoprotein receptors are unable to remove cholesterol from the

45、blood effectively.Researchers are working to identify and characterize additional genes that may influence cholesterol levels and the risk of heart disease in people with hypercholesterolemia.Read more about the APOB, LDLR, LDLRAP1, and PCSK9 genes. How do people inherit hypercholesterolemia?Most ca

46、ses of high cholesterol are not caused by a single inherited condition, but result from a combination of lifestyle choices and the effects of variations in many genes.Inherited forms of hypercholesterolemia resulting from mutations in the LDLR, APOB, or PCSK9 gene have an autosomal dominant pattern

47、of inheritance. Autosomal dominantinheritance means one copy of an altered gene in each cell is sufficient to cause the disorder.An affectedtypically inherits one altered copy of te from an affected parentand one normal copy of te from the other parent.Rarely, awith familial hypercholesterolemia is

48、born with two mutated copies of theLDLR gene. This situation occurs when thehas two affected parents, each of whompasses on one altered copy of te. The presence of two LDLR mutations results in amore severe form of hypercholesterolemia that usually appears in childhood.When hypercholesterolemia is c

49、aused by mutations in the LDLRAP1 gene, the condition is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means the condition results from two altered copies of the gene in each cell. The parents of an individual with autosomal recessive hypercholesterolemia each carry on

50、e copy of the altered gene, but their blood cholesterol levels are usually in the normal range.Where can I find information about diagnosis or management of hypercholesterolemia? These resources address the diagnosis or management of hypercholesterolemia and may include treatment providers.GeneFacts

51、: Familial Hypercholesterolemia: DiagnosisThis link leads to a site outside Genetics Home Reference.GeneFacts: Familial Hypercholesterolemia: ManagementThis link leads to a site outside Genetics Home Reference.Gene Review: Familial HypercholesterolemiaThis link leads to a site outside Genetics Home

52、Reference.Genetic Testing Registry: Familial hypercholesterolemiaThis link leads to a site outside Genetics Home Reference.Genetic Testing Registry: Hypercholesterolemia, autosomal dominant, 3This link leads to a site outside Genetics Home Reference.Genetic Testing Registry: Hypercholesterolemia, au

53、tosomal dominant, type BThis link leads to a site outside Genetics Home Reference.Genetic Testing Registry: Hypercholesterolemia, autosomal recessiveThis link leads to a siteoutside Genetics Home Reference.MedlinePlus Encyclopedia: Familial hypercholesterolemiaThis link leads to a site outside Genet

54、ics Home Reference.MedlinePlus Encyclopedia: High blood cholesterol and triglyceridesThis link leads to a site outside Genetics Home Reference.MedlinePlus Encyclopedia: XanthomaThis link leads to a site outside Genetics Home Reference.You might also find information on the diagnosis or management of

55、 hypercholesterolemia in Educational resources and Patient support.General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.To locate a healthcare

56、provider, see How can I find a genetics professional in my area? in the Handbook.Where can I find additional information about hypercholesterolemia?You may find the following resources about hypercholesterolemia helpful. These materialsare written for teral public.MedlinePlus - Health information (5

57、 links)Genetic and Rare Diseases Information CenterThis link leads to a site outside Genetics Home Reference. - Information about genetic conditions and rare diseasesAdditional NIH Resources - National Institutes of HealthNational Heart, Lung, and Blood InstituteThis link leads to a site outside Gen

58、etics Home Reference.Educational resources - Information pages (9 links) Patient support - For patients and families (4 links)You may also be interested in these resources, which are designed for healthcare professionals and researchers.Gene ReviewsThis link leads to a site outside Genetics Home Reference. - Clinical summary Genetic Testing Registry - Repository of genetic test information (4 links) ClinicalTThis link leads to a site outside Genetics Home Reference. -