| Nontraditional Inheritance | 非傳統(tǒng)性遺傳 |
| In addition to the traditional inheritance patterns, several other mechanisms have been described. They involve genetically determined structures and can produce various disorders. | 除了傳統(tǒng)遺傳模式外,還有一些其他的機(jī)制.它們涉及遺傳學(xué)上確定的結(jié)構(gòu)并可產(chǎn)生各種病癥. |
| Mosaicism: Mosaicism is the presence of >= 2 cell lines differing in genotype or karyotype but derived from one zygote. Mutations are likely to occur during the cell divisions of any large multicellular organism even though the genetic apparatus of cell division is usually accurate and many mechanisms exist to repair mistakes made during replication. It is estimated that each time a cell divides, four or five changes occur in the genome. Thus, any large multicellular organism will have subclones of cells having a slightly different genetic makeup. These somatic mutations （ie, mutations during mitotic cell division） may not lead to disease but to disorders in which patchy changes occur. Molecular genetic techniques have shown mutations in the abnormal cells involved in a patch compared with the normal surrounding supporting tissues. For example, in McCune-Albright syndrome, there are patchy dysplastic changes in the bone, abnormalities of endocrine glands, patchy pigmentary changes, and occasionally abnormalities in the heart or liver. Persons with these abnormalities in all cells would die, so the condition would not be passed on to the next generation, but they survive because normal tissue supports the abnormal tissue. Occasionally, in a single-gene disorder, a parent seems to have a milder form but is actually a mosaic; their more severely affected child would have received a germ cell with the mutant allele and thus would have the abnormality present in every cell. Chromosomal mosaicism occurs in some embryos and can be demonstrated in the placenta on chorionic villus sampling. Most chromosomally abnormal embryos and fetuses abort spontaneously. However, the development of normal cells may support certain chromosomal abnormalities, allowing offspring to be born alive. | 鑲嵌性 鑲嵌是指體內(nèi)有從同一個(gè)合子衍生出來的兩個(gè)或更多的不同基因型或核型的細(xì)胞系.雖然細(xì)胞分裂的遺傳系統(tǒng)一般是精確的并且有許多機(jī)制可對(duì)復(fù)制過程中產(chǎn)生的錯(cuò)誤進(jìn)行修復(fù),任何大的多細(xì)胞機(jī)體在細(xì)胞分裂中仍可出現(xiàn)突變.據(jù)估計(jì),每次細(xì)胞分裂,基因組中會(huì)出現(xiàn)4~5個(gè)變化.因此,任何大的多細(xì)胞機(jī)體會(huì)有一些基因構(gòu)造略有不同的細(xì)胞亞克隆.這些體細(xì)胞突變（即有絲分裂時(shí)的突變）可以不引起疾病,而只是一些紊亂,出現(xiàn)一些斑塊狀變化.分子遺傳學(xué)技術(shù)可以把斑塊中的異常細(xì)胞的突變從周圍正常的支持組織中區(qū)別出來.例如在McCune-Albright綜合征中,骨中有發(fā)育不良斑塊,還有內(nèi)分泌腺異常,色素斑以及偶有心或肝的異常.如果所有細(xì)胞均有此類異常必死無疑,所以該病癥不會(huì)傳給第二代.然而這些病人可以存活,因?yàn)檎＝M織支持著異常組織.偶爾,在單基因遺傳病中,父母一方是輕型鑲嵌體.其更為嚴(yán)重受累的孩子可能得到一個(gè)帶有突變等位基因的生殖細(xì)胞,因而在每一細(xì)胞中均有異常.染色體鑲嵌性見于某些胚胎并可在胎盤中的絨毛膜標(biāo)本上被顯示.大部分染色體異常的胚胎和胎兒均自發(fā)流產(chǎn).然而,正常細(xì)胞的發(fā)育可以支持某些染色體異常者而使后代活著出生. |
| Genomic imprinting: Genomic imprinting is the differential expression of genetic material depending on whether it has been inherited from the father or mother. Genomic imprinting is tissue-specific and time-in-development-specific. Bi-allelic or biparental expression of alleles may be present in some tissues and uniparental expression in other tissues. Angelman syndrome and Prader-Willi syndrome can both be produced by deletions of chromosome 15. Groups of specific genes exist in close proximity on chromosome 15 with only paternal or maternal expression. Depending on whether the deleted chromosome is paternally or maternally inherited, a different syndrome will be produced. | 基因組印跡 基因組印跡是遺傳物質(zhì)根據(jù)其來自父親還是母親而出現(xiàn)的不同表達(dá).基因組印跡是組織特異的和時(shí)間-發(fā)育特異的.某些組織中可能出現(xiàn)等位基因的雙等位基因或雙親表達(dá),其他組織中是單親表達(dá).Angelman綜合征和Prader-Willi綜合征都可因第15號(hào)染色體缺失而產(chǎn)生.特異基因存在于第15號(hào)染色體的近端,只具有父源或母源表達(dá).根據(jù)缺失染色體來自父親還是母親而出現(xiàn)不同的綜合征. |
| Many areas on several chromosomes have this type of parent-of-origin effect. The involved genes seem to be related to growth and behavior in early development. Some of these genes are also involved in tumors and cancers. Genomic imprinting must be considered in disorders that appear to have skipped a generation. | 好幾條染色體的許多區(qū)域都有這種親源效應(yīng).涉及的基因似與早期發(fā)育的生長和行為有關(guān).其中某些基因還與腫瘤和癌的發(fā)生有關(guān).當(dāng)遺傳性病癥跳越一代下傳時(shí),必須考慮作遺傳印跡檢查. |
| Uniparental disomy: Uniparental disomy occurs when two chromosomes of a pair are inherited from only one parent. This is very rare and is thought to involve trisomy rescue; ie, the zygote started off as a trisomy and one of the three chromosomes was lost, leading to uniparental disomy in 1/3 of cases. Imprinting effects may be seen because genetic information from the other parent is absent. In addition, if the same chromosome is in duplicate （isodisomy） and that chromosome carries an abnormal allele for an autosomal recessive disorder, a person with uniparental disomy can have an autosomal recessive disorder although only one parent is a carrier. Vestigial chromosomal abnormalities in some tissues must be considered in the presence of uniparental disomy. | 單親二體 當(dāng)同一對(duì)的兩條染色體都來自父親一方時(shí)可出現(xiàn)單親二體.這是很罕見的并被認(rèn)為還涉及三體挽救,即合子開始時(shí)為三體,而三條染色體中的一條丟失后在1/3的情況下導(dǎo)致單親二體.印跡效應(yīng)可以顯示,因?yàn)闆]有來自父母另一方的遺傳信息.此外,假如相同的染色體為復(fù)制品（同源二體）,而染色體又帶有常染色體隱性遺傳病的一個(gè)異常等位基因,那么這位帶有單親二體的人可能會(huì)出現(xiàn)常染色體隱性遺傳病,盡管父母中只有一方是攜帶者.在有單親二體時(shí),必須考慮到某些組織中的殘余染色體異常. |
| Triplet repeat, unstable mutations: A triplet repeat is an unusual type of mutation in which a triplet of nucleotides increases in number within a gene （a normal gene has relatively few tandem triplet repeats）. This type of mutation has been recognized to occur in several disorders, particularly those involving the CNS. When the gene is transmitted from one generation to the next, or sometimes within the body as cells divide, the triplet repeat can expand and enlarge to a point at which the gene stops functioning normally. Examples include myotonic dystrophy, Huntington's disease, fragile X mental retardation, and several other neurologic disorders. The number of repeats may increase dramatically in the formation of germ cells or in certain tissues as the embryo and fetus develop. Expansion may be greater when transmitted from one parent （eg, the mother in myotonic dystrophy, the father in Huntington's disease）; thus, a parent-of-origin effect and anticipation can be observed. This type of mutation is detected by molecular studies. | 三聯(lián)體重復(fù)序列,不穩(wěn)定突變 三聯(lián)體重復(fù)序列是一種不常見的突變類型,發(fā)生時(shí),在基因內(nèi)的核苷酸三聯(lián)體的數(shù)目增加（正?；蛑挥邢鄬?duì)很少的串聯(lián)三聯(lián)體重復(fù)序列）.此種突變?cè)娪谀承┎“Y,特別是涉及中樞神經(jīng)系統(tǒng)者.當(dāng)基因從一代傳到下一代,或有時(shí)在體內(nèi)當(dāng)細(xì)胞分裂時(shí),三聯(lián)體重復(fù)序列可以擴(kuò)張?jiān)龃蟮绞够虿荒苷０l(fā)揮功能的地步.例子有肌強(qiáng)直性營養(yǎng)不良,Huntington病,脆性X智力障礙和其他一些神經(jīng)科疾病.在生殖細(xì)胞形成過程中或胚胎和胎兒發(fā)育時(shí)的某些組織中,重復(fù)序列的數(shù)目可以明顯增加.如果突變系從父母一方傳來（例如母親有肌強(qiáng)直性營養(yǎng)不良,父親有Huntington病）,則擴(kuò)張可以更厲害.因此,可以觀察到一種親源效應(yīng)和早現(xiàn)現(xiàn)象.此種突變可由分子技術(shù)檢出. |
| Anticipation: Anticipation occurs when a disorder has an earlier age of onset and severity of expression in each successive generation. It may occur because a parent is a mosaic, and the child has the full mutation in all cells. Triplet repeat expansion may demonstrate anticipation when the number of repeats increases with each generation. | 早現(xiàn) 早現(xiàn)是指病癥在逐代傳遞過程中發(fā)病年齡越來越早,病情越來越重.它的出現(xiàn)是因?yàn)楦改敢环绞氰偳扼w,孩子的所有細(xì)胞都有完全突變.當(dāng)三聯(lián)體重復(fù)序列的數(shù)目逐代增加時(shí),它的擴(kuò)張就可表現(xiàn)出早現(xiàn)之象 |
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