DIAGNOSIS OF DOWN-SYNDROME AND OTHER ANEUPLOIDIES USING QUANTITATIVE POLYMERASE CHAIN-REACTION AND SMALL TANDEM REPEAT POLYMORPHISMS
DIAGNOSIS OF DOWN-SYNDROME AND OTHER ANEUPLOIDIES USING QUANTITATIVE POLYMERASE CHAIN-REACTION AND SMALL TANDEM REPEAT POLYMORPHISMS
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DOI：
10.1093/hmg/2.1.43
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发表时间：
1993-01-01
影响因子：
3.5
通讯作者：
MANSFIELD, ES
中科院分区：
文献类型：
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作者：
MANSFIELD, ES
35岁以上的孕妇通常会接受筛查和核型分析，以检测唐氏综合征和某些其他非整倍体，因为这些疾病的风险随着母亲年龄的增长呈指数级增加。然而，只有对高危妊娠进行染色体核型分析才具有成本效益，大量剩余的非整倍体病例未被发现。我们描述了一种快速，廉价的方法来检测三体性使用多态性小串联重复序列（STR）标记和聚合酶链反应（PCR）扩增单核细胞DNA。从21三体、18三体和X三倍体综合征患者身上获得的STR模式与对照组不同。多态性三体性基因型显示三个相同强度的片段峰或2：1剂量比的两个片段。此外，特纳综合征（45，X0）DNA可以与正常男性DNA区分开来，因为它不能扩增Y染色体特异性PCR标记，而只含有单剂量的X特异性STR标记。STR标记物的峰高和峰面积的定量分析表明，两个峰模式分离成完全不重叠的组。大多数STR标记的高水平杂合性导致杂合对照和具有多个等位基因的三体模式占优势，这是最容易区分的模式。纯合性，因此一个无信息的STR模式，是更常见的控制比三体样品。我们预计每条染色体上只有三个STR标记的信息量应该超过99%。
Pregnant women over 35 years of age are routinely offered screening tests and karyotyping to detect Down syndrome and certain other aneuploidies because the risk of these disorders increases exponentially with maternal age. It is, however, only cost-effective to karyotype high-risk pregnancies and a substantial number of remaining aneuploidy cases go undetected. We describe a rapid, inexpensive method to detect trisomy using polymorphic small tandem repeat (STR) markers and the polymerase chain reaction (PCR) to amplify amniocyte DNA. STR patterns obtained on patients with trisomy 21, trisomy 18 and triplo-X syndromes are distinct from controls. Polymorphic trisomy genotypes either show three fragment peaks of equal intensity or two fragments at a 2:1 dosage ratio. In addition, Turner syndrome (45, X0) DNA can be distinguished from normal male DNA because it fails to amplify a Y-chromosome specific PCR marker vet contains only a single dose of X-specific STR markers. Quantitative analysis of peak heights and areas from STR markers show that the two peak patterns separate into completely non-overlapping groups. The high level of heterozygosity of most STR markers result in a predominance of heterozygous controls and trisomy patterns with multiple alleles, the easiest patterns to differentiate. Homozygosity, and hence an uninformative STR pattern, is more common in controls than in trisomy samples. We anticipate as few as three STR markers per chromosome should be over 99% informative.