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  • 遗传病诊断和治疗 -- -- 高级

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    Can you cure genetic disorders?
    ::你能治愈遗传疾病吗?

    Currently it is difficult. To truly "cure" a , you would have to replace the mutant with non mutant DNA. If only it were as easy as just injecting the nonmutant DNA through a syringe.
    ::目前这很难。 要真正“ 孵化 ” , 您就必须用非变种DNA替换变种人。 如果这和通过注射器注射非变种DNA一样容易的话 。

    Diagnosis and Treatment of Genetic Disorders
    ::遗传病诊断和治疗

    If someone has a rare genetic disease in her family, can she still have a baby? Is she predisposed to pass that phenotype along to her child? These are questions for a professional trained in human genetics . A geneticist and genetic counselor are usually involved in the diagnosis and treatment of human genetic disorders. Families with a genetic disease are referred to a genetic counselor, especially when they wish to determine a baby’s likelihood of inheriting the genetic disease.
    ::如果某个家庭有罕见的遗传疾病,她是否仍然有孩子?她是否愿意将这种苯型传给孩子?这是受过人类遗传学专业培训的人的问题。 遗传学家和遗传顾问通常参与人类遗传病的诊断和治疗。 有遗传病的家庭被转介给遗传顾问,特别是当他们想确定婴儿继承遗传病的可能性时。

    Individuals or their families at risk of inheriting a genetic disorder have many questions.
    ::有可能继承遗传障碍的个人或其家庭有许多问题。

    • What exactly is a genetic disorder?
      ::什么是基因障碍?
    • How does a person get it?
      ::一个人如何得到它?
    • Can it be passed onto the next generation?
      ::能传给下一代吗?
    • Can it be treated?
      ::能治疗吗?
    • What are the symptoms?
      ::症状是什么?
    • Do the symptoms get worse with age?
      ::年龄的症状会恶化吗?

    These and many more questions are where a genetic specialist, such as a genetic counselor can help. Genetic counseling is the process by which individuals or their families who are at risk of an inherited disorder, are counseled on many different aspects of the disorder. Genetic counseling may be necessary at any time throughout life, from before to . Before pregnancy, genetic counseling would be appropriate for at risk individuals who are planning a family, such as when one or both individuals are either carriers or have a certain genetic trait . During pregnancy, genetic counseling is necessary for couples if the woman will be over 35 years of age at the time of delivery, if prenatal testing is recommended for any reason, or if an abnormality is noted on an ultrasound or other test. After birth, genetic counseling is appropriate if a birth defect is detected. During childhood , genetic counseling is appropriate if the child manifests any signs of developmental delay or a genetic syndrome, and in adulthood, genetic counseling is appropriate if signs of an adult onset genetic disorder is detected. During genetic counseling, individuals are advised of the consequences and nature of the disorder, the of developing or transmitting the disorder, and the options open to them in management and family planning in order to make appropriate decisions. In terms of the actual diagnosis of the disease, molecular analysis may be necessary. Molecular analysis or testing is discussed in the concepts.
    ::在怀孕期间,如果孕妇在分娩时超过35岁,如果因任何原因建议进行产前检查,或者如果在超声波或其他测试中发现异常情况,则需要进行遗传咨询; 出生后,如果发现出生缺陷,遗传咨询是适当的; 在童年时期,如果儿童表现出发育迟缓或遗传综合症的任何迹象,遗传咨询是适当的; 在成年时期,如果发现成人突发遗传障碍的迹象,遗传咨询是适当的; 在遗传咨询期间,个人被告知疾病的后果和性质、发育或传播紊乱症,以及在管理和计划生育中向她们开放的选择,以便做出正确的诊断。

    Prenatal Diagnosis
    ::产前诊断

    "Is it possible to test the developing baby for potential genetic problems? Do you need to remove some of the baby's DNA? How do you do that?"
    ::“能否对发育中的婴儿进行潜在的基因问题测试?你需要移除婴儿的DNA吗?你怎么做到的?”

    These questions are appropriate for a geneticist. Sometimes, to make sure the baby is developing properly, prenatal diagnosis is necessary. Prenatal diagnosis refers to the diagnosis of a disease or condition before the baby is born. The reason for prenatal diagnosis is to detect birth defects such as neural tube defects, abnormalities, genetic diseases and other conditions. It can also be used to determine the sex of the unborn baby, though this can usually be determined by ultrasonography (ultrasound).
    ::这些问题适合遗传学家。有时,为了确保婴儿发育正常,产前诊断是必要的。产前诊断是指对婴儿出生前的疾病或状况的诊断。产前诊断的理由是发现先天缺陷,如神经管缺陷、异常、遗传疾病和其他状况。还可以用来确定胎儿的性别,尽管这通常可以由超声波(超声波)确定。

    Diagnostic prenatal testing can be by invasive methods or non-invasive methods. Non-invasive methods are much less risky to the patient. Non-invasive methods can only evaluate the risk of a condition and cannot actually determine if the fetus has a condition. Non-invasive techniques include examinations of the mother's womb through ultrasonography and analysis of maternal serum. If an abnormality is indicated by a non-invasive procedure, a more invasive technique may be employed to gather more information. Amniocentesis and chorionic villus sampling (CVS) are invasive procedures. These involve probes or needles that are inserted into the placenta . Amniocentesis can be done from about 14 weeks up to about 20 weeks of the pregnancy and CVS can be done earlier, between 9.5 and 12.5 weeks, but is slightly more risky to the unborn child.
    ::产前诊断检测可以是侵入性方法或非侵入性方法。非侵入性方法对病人的风险要小得多。非侵入性方法只能评估病情风险,不能实际确定胎儿是否有病症。非侵入性技术包括通过超声波检查母亲的子宫,分析产妇血清。如果非侵入性程序显示异常,可以使用一种更具侵入性的技术来收集更多信息。羊胸和胆囊取样是侵入性程序。这些方法涉及插入胎盘的探针或针头。从怀孕14周到大约20周的时间里,可以在9.5周到12.5周之间提前进行,但对于未出生的孩子来说风险略高。

    During Amniocentesis a small amount of amniotic fluid , which contains fetal , is extracted from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for genetic abnormalities. Amniocentesis is not performed for every pregnancy, but is generally done when an increased risk of genetic defects in the fetus is indicated, by mother's age (over 35 years is common), family history of genetic defects, or other factors.
    ::在亚尼诺森特斯期间,有少量含胎儿的羊水,从发育中的胎儿周围的羊水或羊水囊中提取,对胎儿DNA进行基因异常检查,不是每次怀孕都进行亚尼诺森特斯,但通常在胎儿遗传缺陷风险增加的情况下进行,根据母亲年龄(35岁以上)、家庭遗传缺陷历史或其他因素,根据母亲年龄(35岁以上),家庭遗传缺陷历史或其他因素,进行这种检查。

    Chorionic villus sampling (CVS) involves removing a sample of the chorionic villus (placental tissue) and testing it. It is generally carried out only on pregnant women over the age of 35 and those whose offspring have a higher risk of Down syndrome and other chromosomal conditions. The advantage of CVS is that it can be carried out 10-12 weeks after the last period, earlier than amniocentesis.
    ::胆碱酯酶采样(CVS)包括取出和测试一个乳腺组织样本,一般只对35岁以上的孕妇和其后代患唐氏综合症和其他染色体病的风险较高的孕妇进行,其优点是可以在上一个时期之后10至12周进行,比羊膜炎早10至12周。

    DNA from the developing baby may be isolated from either an amniocentesis or CVS. A karyotype may be created from fetal chromosomes following either procedure, or a specific may be analyzed.
    ::从发育中的婴儿身上提取的DNA可以从羊膜中分离出来,也可以从CVS中分离出来。 可以按照两种程序,从胎儿染色体中产生甲状腺型,或者可以分析具体的染色体。

    Gene Therapy
    ::基因治疗

    So, how do you treat genetic disorders? If medically possible, each manifestation of a genetic disease can be treated separately. But is there a way to use genetics to treat the root cause of the disease – that is, to fix the mistake in the DNA?
    ::那么,你如何治疗遗传病?如果医学上可能的话,遗传病的每一种表现都可以分开治疗。 但是,有办法利用遗传学治疗该疾病的根源吗? 也就是说,修复DNA中的错误?

    Gene therapy is the insertion of a new gene into an individual’s cells and tissues to treat a disease, replacing a mutant disease-causing with a normal, non-mutant allele. Although the technology is still in its early stages of , it has been used with some success.
    ::基因疗法是将新基因插入个人细胞和组织以治疗疾病,用正常的非变异性通灵替代致病。 尽管该技术仍处于初级阶段,但已被成功使用。

    There are a number of mechanisms used to replace or repair a defective gene in gene therapy.
    ::在基因疗法中,使用若干机制取代或修复有缺陷的基因。

    • A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is most common.
      ::正常基因可插入基因组内一个非特定地点,以取代不起作用的基因。
    • An abnormal gene could be replaced by a normal gene through homologous recombination .
      ::异常基因可以通过同质重组被正常基因所取代。
    • The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal, non-mutant state.
      ::异常基因可以通过选择性反向突变加以修复,使基因恢复到正常的非变异状态。
    • The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.
      ::某一基因的管制(某一基因的开关或关闭的程度)可以改变。

    As stated above, the most common gene therapy approach is to replace a disease-causing allele with a normal allele. To deliver the new allele to the appropriate cells, a carrier, called a vector , must be used. Currently, the most common type of vectors are that have been genetically altered to carry normal human DNA, and not to result in any phenotypes associated with the virus. As viruses have evolved a robust method of delivering their viral genes to human cells, scientists have tried to develop (and are continuing to develop) methods to take advantage of this process, and have these vectors insert human DNA into target cells . Scientists have manipulated the viral genome to remove disease-causing genes and insert therapeutic human genes ( Figure ). For obvious reasons, this is currently a field of intense biomedical research.
    ::如上所述,最常见的基因疗法方法是用正常的球菌来取代一种致病的球菌。为了将新的球菌送入适当的细胞,必须使用一个叫做矢量的载体。目前,最常见的矢量类型是转基因,以携带正常的人类DNA,而不是产生与病毒有关的任何苯型。随着病毒发展出一种强有力的方法,将病毒基因传送给人类细胞,科学家们试图开发(并正在继续开发)利用这一过程的方法,并将人类的DNA插入目标细胞。科学家们操纵病毒基因组去掉疾病基因并插入治疗性人类基因(图 ) 。由于明显的原因,这是目前密集生物医学研究的一个领域。

    lesson content

    Gene Therapy using a viral vector. The new gene is inserted into the viral genome, the virus binds to the cell membrane and enters the cell by endocytosis. The viral genome, containing the new gene is injected into the cell nucleus, where the viral DNA is transcribed, starting the process of protein synthesis.
    ::使用病毒媒介的基因治疗。 新的基因被插入病毒基因组,病毒与细胞膜结合,通过内分泌进入细胞。 含有新基因的病毒基因组被注入细胞核,病毒DNA被转录到细胞核中,开始蛋白质合成过程。

    A patient's target cells, such as liver or lung cells are infected with the genetically altered virus. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional product from the therapeutic gene should restore the target cell to a normally functioning phenotype. To date, this process has had limited success, but further research should improve results.
    ::病人的目标细胞,如肝脏或肺细胞,会感染转基因病毒,然后将含有治疗性人类基因的遗传材料卸入目标细胞。从治疗性基因中产生功能性产品,应该将目标细胞恢复到正常功能性的苯型。迄今为止,这一过程取得了有限的成功,但进一步研究应该改善结果。

    Severe Combined Immunodeficiency
    ::严重混合 免疫机能丧失综合症

    Severe Combined , or SCID, is a heritable immunodeficiency - a genetic disorder that cripples the immune system . It is also known as the "bubble boy" disease, named after David Vetter, SCID’s most famous patient who lived for over 12 years in a sterilized environment, just like living inside a “bubble.” SCID affects about 1 in 100,000 live births. These babies, if untreated, usually die within one year due to severe, recurrent infections. Treatment options have improved considerably and include bone marrow transplants and gene therapy. Children no longer have to live inside a bubble as did David Vetter, who was placed inside his sterile bubble about 10 seconds after birth. He died 15 days after he left his sterile environment, due to an undetected virus in the bone marrow transplant. David was one of the first bone marrow recipients.
    ::严重综合症(SCID)是一种遗传性免疫缺陷,是一种遗传障碍,它使免疫系统瘫痪。它也被称为“泡泡男孩”疾病,以SCID最著名的病人大卫·威特(David Vetter)的名字命名。 大卫·维特(David Vetter)在绝育环境中生活了12年以上,就像生活在“泡泡中 ” 。 SCID影响大约十万个活产儿。 这些婴儿,如果得不到治疗,通常会在一年内死于严重、常见的感染。 治疗方案已经大有改进,包括骨髓移植和基因治疗。 孩子们不再像David Vetter那样生活在泡沫中,他在出生后10秒左右被放入无菌泡沫中。 他离开不育环境后15天去世,因为骨髓移植中未发现病毒。 大卫是第一个骨髓移植者之一。

    More recently gene therapy has proved successful in treating SCID. Insertion of the correct gene into cells of the immune system should correct the problem. Trials started in 1990, and in 1999, the first SCID patients were detected with functional immune systems. Due to some complications these trials had to be stopped, but these issues seem to have been resolved. Since 1999, gene therapy has restored the immune systems of at least seventeen children with the disorder. This raises great hope for other genetic disorders. In your lifetime, it is definitely possible that many genetic disorders may be “cured” by gene therapy.
    ::最近,基因疗法在治疗SCID方面证明是成功的。将正确的基因插入免疫系统的细胞应该能纠正这个问题。1990年和1999年开始的试验是使用功能性免疫系统检测出的首个SCID病人。由于这些试验有些并发症,必须停止,但这些问题似乎已经解决。自1999年以来,基因疗法已经恢复了至少17名患有这种疾病的儿童的免疫系统。这为其他基因疾病带来了巨大的希望。在你的一生中,许多基因疾病都有可能通过基因疗法“治愈 ” 。

    With this technique and its great possibilities, no one can predict what will happen in the future, but it could have profound effects on the future of medicine.
    ::有了这种技术及其巨大的可能性,没有人能够预测未来会发生什么,但它可能对医药的未来产生深远的影响。

    Summary
    ::摘要

    • Prenatal diagnosis refers to the diagnosis of a disease or condition before the baby is born.
      ::产前诊断是指婴儿出生前对疾病或状况的诊断。
    • Amniocentesis and chorionic villus sampling are invasive methods involved in prenatal diagnosis.
      ::在产前诊断中,对羊膜和胆碱酯酶进行抽样检查是侵入性的方法。
    • Gene therapy is the insertion of a new gene into an individual’s cells and tissues to treat a disease, replacing a mutant disease-causing allele with a normal, non-mutant allele.
      ::基因疗法是将新基因插入个人细胞和组织,以治疗疾病,用正常、非变异的异种致病通灵代替异种致病通灵。

    Review
    ::回顾

    1. Why is genetic counseling important?
      ::为什么基因咨询很重要?
    2. What is gene therapy?
      ::什么是基因疗法?
    3. Describe the most common approach to gene therapy.
      ::描述基因治疗的最常见方法。