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  • 遗传疾病 - 高级

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    Is being short-statured inherited?
    ::短暂的继承吗?

    It can be. Achondroplasia is the most common form of dwarfism in humans, and it is caused by a dominant . The mutation can be passed from one generation to the next. Over 95% of unrelated individuals with Achondroplasia have the same mutation, making it one of the most common mutations in the . Why?
    ::可能是的。 亚琴乌狄拉西亚是人类中最常见的侏儒主义形式,它是由占支配地位者造成的。突变可以代代相传。 95%以上的与阿琴乌特拉西亚无关的个人也有相同的突变,使其成为最常见的突变之一。 为什么?

    Mutations and Genetic Disorders
    ::变异和遗传疾病

    Mutations , changes in the or sequence, can have significant phenotypic effects or they can have no effects. What are possible outcomes of some of those mutations. Some can produce genetic disorder . A genetic disorder is a condition caused by abnormalities, such as mutations, in your genes or . Genetic disorders are usually present from conception. These disorders include chromosomal abnormalities, in which the individual has too few or too many chromosomes or chromosomes with large alterations, or diseases due to a mutation in a specific gene. These defective genes are usually inherited from the parents, hence the term hereditary disease or genetic disorder. Genetic disorders can be inherited in a dominant or recessive manner ( Figure and Figure ). Recessive disorders require the inheritance of a defective gene from each parent. The parents are usually unaffected and are healthy carriers of the defective gene.
    ::突变、变异、变异、变异或序列变化,可能具有重大的雌激素效应,也可能不会产生任何影响。其中一些变异可能带来什么结果。有些变异可能产生遗传障碍。遗传障碍是突变、基因变异或遗传障碍等异常造成的。遗传障碍通常是从受孕以来就存在的。这些障碍包括染色体异常,其中个人染色体或染色体变异甚少或过多,或因特定基因突变而导致的疾病。这些有缺陷的基因通常由父母继承,因此称为遗传疾病或遗传障碍。遗传障碍可以以主导或休眠的方式传承(图示和图示)。迟发性障碍要求从每个父母继承有缺陷的基因。父母通常不受影响,并且是缺陷基因的健康携带者。

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    Autosomal Dominant Inheritance. Only one “affected” allele is necessary to result in the “affected” phenotype. For a genetic disease inherited in this manner, only one mutant allele is necessary to result in the phenotype. Achondroplasia (discussed later) is an example of a dominant disorder. Both homozygous and heterozygous individuals will show the phenotype. Homozygous achondroplasia is usually a lethal condition.
    ::自主的多功能继承。 只有一种“ 受到影响的” 外延元素是产生“ 受到影响的” 苯型。 对于以这种方式遗传的遗传性疾病,只有一种变异的外延元素是产生苯型的必需。 Achondopolasia(稍后再讨论)是主导性疾病的一个实例。同性古人和异体zygous人都会显示苯型。同性古人通常是一种致命疾病。

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    Autosomal Recessive inheritance. For a genetic disease inherited in this manner, two mutant alleles are necessary to result in the phenotype. Tay-Sachs Disease (discussed later) is an example of a recessive disorder. Notice that both parents are unaffected carriers of the mutant allele. These unaffected carriers allow the allele to be maintained in the gene pool - the complete set of a population's genes. Even if the allele is lethal in the homozygous recessive condition, the allele will be maintained through heterozygous individuals.
    ::自动衰退的遗传遗产。 对于以这种方式遗传的遗传性疾病, 需要两种变异异异种来导致苯型。 Tay- Sachs 疾病( 稍后讨论) 是休眠紊乱的一个例子。 注意父母双方都是变异异异种的未受感染的携带者。 这些未受感染的携带者允许将异性保留在基因库中 — — 整个人群的基因组。 即使异种在同质虫的休眠状态中是致命的, 该异性也会通过异性突变异体个体来维持。

    How can you, or a geneticist, determine the inheritance pattern of a phenotype ? A , which is essentially a representation of genetic inheritance, is helpful. A pedigree is a chart, much like a family tree, which shows all of the known individuals within a family with a particular phenotype ( Table ). Pedigrees have been discussed in the in Humans concept. Examples of autosomally inherited disorders include cystic fibrosis , Tay-Sachs disease, phenylketonuria, and achondroplasia.
    ::您或一位遗传学家如何确定一种苯型的遗传模式?A基本上是遗传遗传遗产的象征,A很有帮助。Pedigree是一个图表,非常像一棵家庭树,它显示了家庭中所有已知的个人,有特定的苯型(表 ) 。人类概念中已经讨论了Pidigrees。自动遗传性紊乱的例子包括细胞纤维化、Tay-Sachs病、苯丙酮尿和磷酸。

    Inheritance Pattern Description Example
    Autosomal Dominant Only one mutated is needed for a person to be affected by an autosomal dominant disorder . Each affected person usually has one affected parent. There is a 50% chance that a child will inherit the mutated gene. Huntingtons disease, Achondroplasia, Neurofibromatosis 1, Marfan Syndrome, Hereditary nonpolyposis colorectal
    Autosomal Recessive Both copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder . An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Cystic fibrosis, Sickle anemia, Tay-Sachs disease, Spinal muscular atrophy
    X-linked Dominant X-linked dominant disorders are caused by mutations in genes on the X chromosome . Only a few disorders have this inheritance pattern.
    X-linked Recessive X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. A woman who carries an X-linked recessive disorder has a 50% chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the mutated gene. Hemophilia A, Duchenne muscular dystrophy, Color blindness
    Y-Linked Y-linked disorders are caused by mutations on the Y chromosome . Only males can get them, and all of the sons of an affected father are affected. Y-linked disorders only cause infertility, and may be circumvented with the help of some fertility treatments. Male Infertility
    Genetic Disorder Direct Effect of Mutation Signs and Symptoms of the Disorder Mode of Inheritance
    Marfan syndrome defective in connective tissue heart and defects and unusually long, slender limbs and fingers autosomal dominant
    Sickle cell anemia abnormal hemoglobin protein in red blood cells sickle-shaped red blood cells that clog tiny , causing pain and damaging organs and autosomal recessive
    Vitamin D-resistant rickets lack of a substance needed for bones to absorb minerals soft bones that easily become deformed, leading to bowed legs and other skeletal deformities X-linked dominant
    Hemophilia A reduced activity of a protein needed for clotting internal and external bleeding that occurs easily and is difficult to control X-linked recessive

      

     

    Cystic Fibrosis
    ::Cystic 纤维化

    Cystic fibrosis (CF) is an autosomal recessive inheritable disorder caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices, and mucus . Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when individuals have a mutation in both copies of the gene, such that neither gene product works normally. CF is one of the most common life shortening diseases. Diagnosis is usually made in childhood . In the United States, approximately 1 in 3,900 children is born with CF. One in 22 people of European descent are carriers of a mutated CFTR gene. CF mainly affects the lungs and , causing difficulty due to thick mucus production, progressive disability, and for some individuals, premature death.
    ::Cystic Fibrocis (CF) 是一种由称为cyctic fidis Trembrane 行为调节器(FFTR)的基因突变引起的自动溶解性继承障碍。该基因的产物是氯离子渠道,对产生汗水、消化汁和粘结非常重要。虽然大部分没有CFTR基因的人有两份工作副本,但只有一份可以防止Cystic Fibrocis(CF) 。当个人两种基因都发生突变时,CF会发展起来,因此基因产品通常不起作用。CFF是最常见的缩短寿命疾病之一。诊断通常是在童年产生的。在美国,大约3,3,900名儿童出生在CFC。在22个欧洲血统的人中,其中一人是变异性FTR基因的携带者。CFF主要影响肺部,并造成重肌肉生产、逐渐残疾和一些人过早死亡等困难。

    Individuals can be diagnosed prior to birth by genetic testing. Because of CF in the fetus requires each parent to pass on a mutated copy of the CFTR gene and because CF testing is expensive, testing is often initially performed on just one parent. If that parent is found to be a carrier of a CFTR gene mutation, the other parent is then tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations; currently it is not possible to test for each one. As new DNA testing methodologies are developed, testing for more mutations will become more common and less expensive. Testing analyzes DNA for the most common mutations, such as a deletion of amino acid 508 (phenylalenine, also known as ΔF508). If a family has a known uncommon mutation, specific screening for that mutation can be performed. However, it must be noted that because there may be other not yet identified mutations that result in CF, and as not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF.
    ::由于胎儿体内的CF要求父母每人传递FFTR基因变异的复制件,并且由于CF测试费用昂贵,测试通常最初只由父母一方进行;如果发现父母一方是FFTR基因变异的载体,则对另一方父母进行测试,以计算子女变异的风险。CF可能来自一千多种不同的变异;目前无法对每个变异进行测试。随着新的DNA测试方法的开发,对更多的变异的测试将变得更加常见,更便宜。测试分析最常见变异的DNA,例如删除氨酸508(苯丙烯,也称为QF508)。如果一个家庭有已知的突变现象,则可以对该变异进行具体筛选。然而,必须指出,由于可能尚未发现其他导致CFF的变异种,而且目前测试中未发现所有已知的变异种,负屏并不能保证儿童没有CFC。

    Tay-Scahs Disease
    ::Tay-Scahs疾病

    Tay-Sachs disease is a genetic disorder that is fatal in its most common variant, known as Infantile Tay-Sachs disease. Tay-Sachs is an autosomal recessive disorder, requiring the inheritance of a defective gene from each parent. The disease results from the accumulation of harmful quantities of fat in the nerve cells of the brain . Tay-Sachs results from mutations in the HEXA gene located on chromosome 15, which encodes the alpha-subunit of the lysosomal beta-N-acetylhexosaminidase A, which normally breaks down the fat. More than 90 mutations, including substitutions, insertions, deletions, splice site mutations, and other more complex patterns have been characterized in this gene, and new mutations are still being reported. Each of these mutations alters the protein product, inhibiting the function of the enzyme.
    ::Tay-Sachs病是一种致命的遗传疾病,其最常见的变异物称为Neginile Tay-Sachs病。Tay-Sachs是一种自给性休眠紊乱,需要从每个父母继承一个有缺陷的基因。这种疾病是由于大脑神经细胞中积聚了有害数量的脂肪造成的。Tay-Sachs是位于染色体15上的HEXA基因突变的结果,该基因编码了淋巴菌乙型N-乙型乙型乙型乙型乙型乙型乙型乙型乙型乙型六氯环己烷A,通常会分解脂肪。90多起突变,包括替换、插入、删除、螺旋体点突变,以及其他更为复杂的基因模式,而且仍在报告新的突变。这些突变都改变了蛋白产物,抑制了酶的功能。

    Tay-Sachs disease is a rare disease. Unaffected carriers of a Tay-Sachs allele may not know they have the allele. Other autosomal disorders such as cystic fibrosis and sickle cell anemia are far more common. The importance of Tay-Sachs lies in the fact that an inexpensive enzyme assay test was developed. The automation of this analysis has provided one of the first "mass screening" tools in medical genetics . Two unaffected carriers can have a child homozygous for a Tay-Sachs allele, resulting, currently, in a lethal phenotype. Tay-Sachs alleles are maintained in a through these unknowing heterozygous carriers.
    ::Tay-Sachs疾病是一种罕见的疾病。 Tay-Sachs Alles的未受感染的携带者可能不知道他们有这种病菌。其他的自闭性疾病,如细胞纤维化和镰状细胞贫血等,则更为常见。Tay-Sachs的重要性在于开发了廉价的酶测试。这一分析的自动化为医学遗传学提供了第一批“质量筛选”工具之一。两家未受感染的携带者可以拥有一个婴儿同质的Tay-Sachs allele,目前其结果是一种致命的苯型。Tay-Sachs alleles通过这些不知情的异构体携带者在其中保持。

    Anyone can be a carrier of the Tay-Sachs mutation, but the disease is most common among the Ashkenazi Jewish population. About 1 in every 27 members of the Ashkenazi Jewish population carries the Tay-Sachs gene. The analysis and screening for Tay-Sachs has became a research and public health model for understanding and preventing all autosomal genetic disorders. Another genetic disease that is easily analyzed is phenylketonuria.
    ::任何人都可以成为Tay-Sach突变的载体,但这种疾病在阿什克纳齐犹太人口中最为常见,在阿什克纳齐犹太人口中,大约每27人中就有1人携带Tay-Sachs基因,对Tay-Sachs的分析和筛查已成为了解和预防所有自发性遗传疾病的研究和公共卫生模式。另一个容易分析的遗传疾病是苯丙酮尿。

      

     

    Phenylketonuria
    ::苯基氨基氨基苯基氨基磺酸酯

    Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by the inability to metabolize the amino acid phenylalanine. PKU is due to a deficiency in the enzyme phenylalanine hydroxylase (PAH). When PAH is deficient, phenylalanine accumulates and is converted into phenylketones, which can be detected in the urine . Left untreated, this condition can cause problems with brain development, leading to progressive mental retardation and seizures. However, PKU can be treated with a specific diet, one low in phenylalanine. A diet low in phenylalanine and high in tyrosine can bring about a nearly total cure.
    ::Phenylketonuria(PKU)是一种以不能对氨基酸苯丙烯进行代谢为特征的自动休眠性遗传疾病,PKU是由于酶-苯丙胺-羟基酶(PAH)的缺陷造成的,当PAH不足时,苯丙烯累积并转化成苯丙酮,在尿液中可以检测到。如果不加以处理,这种症状可能会造成大脑发育问题,导致智力逐渐迟钝和癫痫。然而,PKU可以接受一种特定的饮食治疗,苯丙烯-苯丙胺含量低,苯丙烯-苯丙烯-苯丙胺含量低和苯丙胺含量高可几乎完全治愈。

    The incidence of PKU is about 1 in 15,000 live births. In the United States PKU is screened at birth as part of a national biochemical screening program, for every baby born in a hospital. Babies born at home may not be screened. If PKU is diagnosed early enough, an affected newborn can grow up with normal brain development, but only by eating a special diet low in phenylalanine for the rest of his or her life. In essence, this is a protein-free diet. This requires severely restricting or eliminating foods high in protein content (containing phenylalanine), such as breast milk, meat, chicken, , nuts, cheese and other dairy products. Starchy foods such as potatoes, bread, pasta, and corn must also be monitored. Many diet foods and diet soft drinks that contain the sweetener aspartame must also be avoided, as aspartame consists of two amino acids: phenylalanine and aspartic acid. Supplementary infant formulas are used in these patients to provide the amino acids and other necessary nutrients that would otherwise be lacking in their diet. Since phenylalanine is required for the synthesis of many proteins, it is necessary to have some of this amino acid, but levels must be strictly controlled. In addition, the amino acid tyrosine, which is normally derived from phenylalanine, must also be supplemented.
    ::PKU的发病率约为每15 000名活产婴儿中就有1例。在美国,PKU作为国家生化筛查方案的一部分,对每个在医院出生的婴儿进行出生检查,在家中出生的婴儿可能不会进行筛查。如果PKU诊断得足够早,受影响的新生儿可以随着正常的大脑发育而成长,但只能通过摄入一种特殊饮食低量的苯麻拉尼(苯麻拉尼)在其生命的余生中生长,这实质上是一种无蛋白的饮食。这需要严格限制或消除高蛋白含量的食物(含苯麻拉尼),如母乳、肉类、鸡类、坚果、坚果、奶酪和其他乳制品。斯塔奇食品,如马铃薯、面包、面食和玉米,也可能受到监控。许多含有甜味的饮食食品和软饮料必须避免,因为部分包括两种氨酸酸:苯麻拉尼和片酸。这些病人使用补充婴儿配方奶,以提供氨酸和其他必要的营养素,否则会缺乏这些营养素。由于苯麻黄素通常需要合成,所以必须使用这种蛋白质。

    Achondroplasia
    ::千伏地拉西亚

    Whereas cystic fibrosis, Tay-Sachs, and phenylketonuria are all autosomal recessive disorders, achondroplasia is an autosomal dominant disorder. Achondroplasia is the most common cause of dwarfism in humans. Achondroplasia is a result of an autosomal dominant mutation in the fibroblast growth factor receptor gene 3 (FGFR3), which causes an abnormality of cartilage formation. FGFR3 normally has a negative regulatory effect on . In achondroplasia, the mutated form of the receptor is constitutively active (constantly “turned on”) and this leads to severely shortened bones. Individuals with achondroplasia are heterozygous for the mutation (one mutant copy, one normal copy). Homozygous for the achondroplasia mutation is lethal prior to birth or shortly after birth.
    ::细胞纤维化、Tay-Sachs和苯丙酮尿都是自闭症,而丙磷酸盐则是一种自闭症主导性疾病。亚硫磷是人类中最常见的侏儒症原因。亚硫磷是纤维纤维生长因子受体基因3(FGFR3)中自闭症主要突变的结果,这种突变导致软体形成异常。FGFR3通常对下述情况产生负面的监管影响:在丙烯酸盐中,受体的变异形式具有组织性活性(默认“转变 ”),这导致骨骼严重萎缩。有丙磷酸盐的人是突变的异基因(一种变异复制品,正常复制品1份),在出生前或出生后不久,突变的突变基因是致命的。

    For autosomal dominant disorders, a person with the disorder has a 50% chance of passing on the gene to their offspring. For achondroplasia, this means there will be a 50% chance that each child will have achondroplasia. Since two copies are fatal, if two people with achondroplasia have a child, there is a 25% chance of the child dying shortly after birth, a 50% chance the child will have achondroplasia, and a 25% chance the child will have a normal phenotype. However, in 3 out of 4 cases, people with achondroplasia are born to parents who don't have the condition. This is the result of a new mutation. New achondroplasis mutations are associated with increasing paternal age (over 35 years). Studies have demonstrated that new gene mutations are exclusively inherited from the father and occur during spermatogenesis . More than 98% of achondroplasia is caused by a G to A point mutation at nucleotide 1138 of the FGFR3 gene, which causes a glycine to arginine substitution. This makes this particular nucleotide one of the most, if not the most, mutable base in the human genome.
    ::对于自发性支配性疾病而言,患有紊乱症的人有50%的机会将基因传给其后代。对于阿琼沙拉西亚人,这意味着每个孩子有50%的机会将患乙硫沙拉西亚。由于两本是致命的,如果两个患有乙硫沙拉西亚的人有一个孩子,则两本是致命的,出生后不久儿童死亡的概率为25%,孩子有50%的机会患乙硫沙拉西亚,孩子有25%的机会具有正常的苯型。然而,在4个病例中,有3个病例中,患甲沙沙拉西亚的人是没有这种病症的父母所生的。这是新突变的结果。新阿琼沙拉西亚人突变与日益成年(35岁以上)有关。研究表明,新的基因突变完全由父亲继承,并且发生在精子产生过程中。超过98%的甲沙拉西亚人将有一个正常的苯菌型突变。在Nucleot 1138个病例中,有3个患有乙硫沙拉西亚的人是没有这种病症的人。这是新突变的结果。新的突变的结果是人类的基因,如果是这个基因底系中最容易变。

    There are three other syndromes with a genetic basis similar to achondroplasia: hypochondroplasia, thanatophoric dysplasia, and SADDAN Dysplasia (severe achondroplasia, developmental delay, acanthuses nigricans, a skin condition). Each of these disorders is also caused by a mutation in the FGFR3 gene. Each of the conditions results in a distinct difference in the degree of severity of the phenotype, with hypochondroplasia having the mildest phenotype and thanatophoric dysplasia being a lethal condition.
    ::另有三种遗传性综合症,类似于甲状腺瘤:甲状腺缺水、甲状腺紊乱症和SADDDAN病状(严重甲状腺衰竭、发育迟缓、胃癌、皮肤状况),这些疾病都是由FGFR3基因突变引起的,每种情况都导致苯型严重性区别,而甲状腺缺血症是一种最轻的苯型,亚原子畸状是致命性疾病。

    Other genes in which mutations cause a phenotypic spectrum of disease include the type I and type II collagen genes, among others. Mutations in the type I collagen genes result in bone disorders, specifically the spectrum of osteogenesis imperfecta, or brittle bone disease. Mutations in the type II collagen disease result in disorders of cartilage, including Achondrogenesis type II, hypochondrogenesis, Kniest Dysplasia, the SEDs (spondyloepiphyseal dysplasia) and Stickler Syndrome.
    ::突变导致胎儿疾病的其他基因包括第一类和第二类科兰基因等。一类科兰基因的突变导致骨骼紊乱,特别是骨骼不全或易碎骨疾病。二类科兰病的突变导致骨骼紊乱,包括二类阿乔因、低分泌产生、Knest Dysplasia、SEDs(血压不全症)和粘合器综合症。

    Treatment
    ::治疗治疗治疗

    The symptoms of genetic disorders can sometimes be treated, but cures for genetic disorders are still in the early stages of development. One potential cure that has already been used with some success is . This involves inserting normal genes into cells with mutant genes. 
    ::基因紊乱症状有时可以治疗,但基因紊乱的治疗仍处于早期发育阶段,一种已经成功使用的潜在治疗方法就是:将正常基因与变种基因植入细胞。

    Summary
    ::摘要

    • In humans many genetic disorders are inherited in a recessive manner.
      ::许多遗传性疾病在人类中是以休眠的方式遗传的。
    • Genetic diseases may also be dominantly inherited, such as with achondroplasia.
      ::遗传疾病也可能是主要遗传性疾病,如亚沙粒病。
    • Genetic diseases may be due to specific mutations within a gene or to large chromosomal abnormalities.
      ::遗传疾病可能是由于基因内的特定突变或因大染色体异常所致。

    Review
    ::回顾

    1. What is a genetic disease?
      ::什么是遗传病?
    2. Describe how a mutation can lead to a genetic disease. Give an example.
      ::描述突变如何导致遗传疾病。举个例子。
    3. How are genetic diseases usually inherited?
      ::遗传疾病通常如何遗传?