CN103069004A - 一种细胞染色体分析方法 - Google Patents
一种细胞染色体分析方法 Download PDFInfo
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
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Abstract
Description
Claims (7)
- 权 利 要 求1. 一种通过测序分析细胞染色体的方法, 其包括以下步驟: a.将获自细胞的 DNA分子随机打断, 得到一定大小的 DNA片 段并测序;b.将步驟 a中测定的 DNA序列与人类基因组参考序列进行严 格比对, 得到所测 DNA序列定位于具体染色体的信息;c.对应于特定染色体 N, 确定所测 DNA序列中定位于该染色 体上的唯一位置的序列的数量总和, 进而得出对应于该染色体 N 的 ChrN% , 即所测 DNA序列中定位于该染色体 N上的唯一位置的 序列的数量总和占所测 DNA序列中定位于所有染色体上的唯一位 置的序列的数量总和的比例:ChrN%=定位于特定染色体 N上的唯一位置的序列的数量总和 / 定位于所有染色体上的唯一位置的序列的数量总和;d.将该染色体的 ChrN%与来自标准细胞中对应染色体的 ChrN%进行比较,确定所述细胞的该奈染色体数量与标准细胞是否 存在差异。
- 2. 权利要求 1所述的方法, 其中步骤 b中所述严格比对是指 不容错的、 定位于人类基因组参考序列上的唯一位置的比对; 其 中所述的人类基因組序列参考序列是人类基因组中经过屏蔽掉重 复序列后所得到的序列。
- 3. 权利要求 1所述的方法, 其中步骤 d中所述细胞样本中特 定染色体数量与标准细胞是否存在差异是通过绘制箱式图方法确 定的,其中将细胞样本中 ChrN%位于超出四分位数差 1. 5倍 - 3倍或 者 3倍以上的四分位数差之间的异常值对应的样本,认定为其染色 体数量与标准细胞存在差异。
- 4. 权利要求 1所述的方法, 其中步驟 d中所述细胞的特定染 色体数量与标准细胞是否存在差异是用反映受检细胞样本 ChrN% 与标准细胞样本 ChrN°/。的偏离程度 z scoreXhrN来确定的, 如果 z score— ChrN绝对值大于等于 3, 所述细胞样本对应的特定染色体的 数量与标准细胞相比存在差异。
- 5. 权利要求 4所述的方法, 其中所述 z score_ChrN= (受检样本特定染色体的 ChrN% ― 特 定染色体 ChrN%平均值 (mean_ChrN% ) ) / ChrN%平均值标准差 ( S. D. _ChrN% ) ;其中所述特定染色体 ChrN 均值可根据来自至少 10个, 例 如至少 20个标准细胞样本的该染色体 ChrN%确定;其中所述特定染色体 ChrN 均值标准差可根据来自至少 10 个, 例如至少 20个标准细胞样本的该染色体 ChrN 均值确定。
- 6. 权利要求 4所述的方法, 其中步裸 d中所述细胞的特定染 色体数量与标准细胞是否存在差异是用 z scoreXhrN与参考值 Z 进行比较加以确定, 其中参考值 Z根据如下方法确定:Z = ( mean_ChrN%) χθ. 5xX % / ( S. D. _ChrN% )其中 X可以为负整数 100 (即 - 100 )至正整数 100之间的任 意整数, 例如 - 100、 - 90、 - 80、 - 70、 - 60、 - 50、 - 40、 -30、 - 20、 - 10、 0、 10、 20、 30、 40、 50、 60、 70、 80、 90、 100; 当 z score-Chr 的绝对值大于等于 3且达到参考值 Z的绝对 值时, 所述细胞的特定染色体数量与标准细胞相比存在 X%的差 异。
- 7. 权利要求 1所述的方法, 其中所述细胞为羊水细胞, 例如 未培养的羊水细胞或培养过的羊水细胞, 优选为未培养的羊水细 胞。
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PCT/CN2010/001230 WO2012019323A1 (zh) | 2010-08-13 | 2010-08-13 | 一种细胞染色体分析方法 |
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CN103069004A true CN103069004A (zh) | 2013-04-24 |
CN103069004B CN103069004B (zh) | 2015-03-11 |
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US (1) | US20130210002A1 (zh) |
EP (1) | EP2604700B1 (zh) |
CN (1) | CN103069004B (zh) |
DK (1) | DK2604700T3 (zh) |
ES (1) | ES2552343T3 (zh) |
HK (1) | HK1185112A1 (zh) |
WO (1) | WO2012019323A1 (zh) |
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CN104205106A (zh) * | 2013-03-28 | 2014-12-10 | 深圳华大基因研究院 | 确定胎儿染色体非整倍性的方法、系统和计算机可读介质 |
CN108256296B (zh) * | 2017-12-29 | 2021-05-25 | 北京科迅生物技术有限公司 | 数据处理装置 |
Citations (1)
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CN101675169A (zh) * | 2006-06-14 | 2010-03-17 | 阿耳特弥斯保健公司 | 使用样品拆分和dna标签进行稀有细胞分析 |
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US7659054B1 (en) * | 2000-05-23 | 2010-02-09 | Nuvelo, Inc. | Methods for genetic analysis of DNA to detect sequence variances |
JP2004531271A (ja) * | 2001-06-22 | 2004-10-14 | ユニバーシティ オブ ジュネーブ | 染色体不均衡により引き起こされる疾患を検出する方法 |
WO2008070249A2 (en) * | 2006-10-30 | 2008-06-12 | Cytotrend (Beijing) Biotech Engineering Co., Ltd | A method of detecting genomic aberrations for prenatal diagnosis |
US20090029377A1 (en) * | 2007-07-23 | 2009-01-29 | The Chinese University Of Hong Kong | Diagnosing fetal chromosomal aneuploidy using massively parallel genomic sequencing |
CA3069081C (en) * | 2008-09-20 | 2023-05-23 | The Board Of Trustees Of The Leland Stanford Junior University | Noninvasive diagnosis of fetal aneuploidy by sequencing |
US8574842B2 (en) * | 2009-12-22 | 2013-11-05 | The Board Of Trustees Of The Leland Stanford Junior University | Direct molecular diagnosis of fetal aneuploidy |
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2010
- 2010-08-13 EP EP10855744.8A patent/EP2604700B1/en active Active
- 2010-08-13 ES ES10855744.8T patent/ES2552343T3/es active Active
- 2010-08-13 CN CN201080068571.9A patent/CN103069004B/zh active Active
- 2010-08-13 WO PCT/CN2010/001230 patent/WO2012019323A1/zh active Application Filing
- 2010-08-13 DK DK10855744.8T patent/DK2604700T3/en active
- 2010-08-13 US US13/640,691 patent/US20130210002A1/en not_active Abandoned
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CN101675169A (zh) * | 2006-06-14 | 2010-03-17 | 阿耳特弥斯保健公司 | 使用样品拆分和dna标签进行稀有细胞分析 |
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US20130210002A1 (en) | 2013-08-15 |
DK2604700T3 (en) | 2015-11-02 |
EP2604700B1 (en) | 2015-07-22 |
EP2604700A4 (en) | 2013-10-30 |
HK1185112A1 (zh) | 2014-02-07 |
WO2012019323A1 (zh) | 2012-02-16 |
CN103069004B (zh) | 2015-03-11 |
ES2552343T3 (es) | 2015-11-27 |
EP2604700A1 (en) | 2013-06-19 |
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Effective date of registration: 20160714 Address after: Beishan Industrial Zone Building in Yantian District of Shenzhen city in Guangdong province 518083 1, 9, 3 and 11 floor of Building 1, 5 floor Patentee after: Shenzhen Huada clinical inspection center Co., Ltd. Address before: Yantian District of Shenzhen City, Guangdong province 518083 Hongan street No. 21 China Comprehensive Park 7 Building 7 layer -14 layer Patentee before: BGI SHENZHEN CO LTD |
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Address after: 518083 1st, 3rd, 4th and 5th floors of 11 buildings in Beishan Industrial Zone, Yantian Street, Yantian District, Shenzhen City, Guangdong Province Patentee after: Shenzhen Huada clinical laboratory center Address before: 518083 Shenzhen Yantian Beishan Industrial Zone Complex Building 1, 9 Floors and 11 1, 3, 5 Floors Patentee before: Shenzhen Huada clinical inspection center Co., Ltd. |
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Address after: 518083 1st, 3rd, 4th and 5th floors of 11 buildings in Beishan Industrial Zone, Yantian Street, Yantian District, Shenzhen City, Guangdong Province Patentee after: Shenzhen Huada Medical Laboratory Address before: 518083 1st, 3rd, 4th and 5th floors of 11 buildings in Beishan Industrial Zone, Yantian Street, Yantian District, Shenzhen City, Guangdong Province Patentee before: SHENZHEN HUADA CLINIC EXAMINATION CENTER |