CN104694663B - Brca基因易感snp位点检测组合物 - Google Patents
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Abstract
本发明公开了BRCA基因易感SNP位点检测组合物,所述BRCA基因易感SNP位点检测组合物包括SEQ?NO:1~SEQ?NO:448的引物。本发明能够一次检测BRCA基因两千多个易感SNP位点,对乳腺癌及卵巢癌相关易感SNP位点具有检测通量高、特异性强、不易污染、安全性高等优点,检测结果具有较好的准确性和重复性,对结乳腺癌和卵巢癌易感人群,尤其是具有这两种癌症家族遗传史的人群有一定的辅助诊断和提示作用。
Description
技术领域
本发明涉及基因检测领域,特别是涉及BRCA基因SNPA位点检测的组合物。
背景技术
乳腺癌是一种严重影响妇女身体健康甚至危及生命的最常见的恶性肿瘤之一。据资料统计,其发病率占全身各种恶性肿瘤的7-10%,在妇女中仅次于子宫癌。乳腺癌的发病常与遗传有关,另外,40-60岁之间,绝经期前后的妇女发病率较高。
乳腺癌可分为散发性和遗传性两大类。其中遗传性乳腺癌约占乳癌发病率的5%-10%。乳腺癌易感基因BRCA1(thefirstfamilialbreastandovariancancersusceptibilitygene)和BRCA2(thesecondfamilialbreastcancersusceptibilitygene)存在可遗传突变,BRCA1或BRCA2突变基因携带者一生中患乳腺癌的危险性估计为90%。此外,BRCA1和BRCA2的突变也和卵巢癌有关。不论有无家族史还是发病年龄,所有卵巢癌中2-6%有BRCA1的突变,3-4%有BRCA2的突变。因此,筛选BRCA基因的突变也来越受到研究者的关注。
BRCA1和BRCA2基因分别定位于17q12-21和13q12-13,编码序列分别为5711bp和10987bp,其表达有一定的组织特异性。BRCA1和BRCA2蛋白分别由1863个氨基酸和3418个氨基酸组成,这两个蛋白都具有Granin蛋白的某些特征。BRCA1/2是两种具有抑制恶性肿瘤发生的基因,在调节人体细胞的复制、遗传物质DNA损伤修复、细胞的正常生长方面有重要作用。拥有这个基因突变的家族倾向于具有高乳腺癌发生率,通常发生在较年轻时,病人的两侧乳房都患癌,且同时患有卵巢癌。如果BRCA1/2基因的结构发生了某些改变,那么它所具有的抑制肿瘤发生的功能就会受影响。截止2013年,已发现的BRCA1/2的突变有数百种之多。有学者总结了BRCA1和BRCA2基因突变相关的癌症的终身风险,显示有BRCA1基因突变者,患乳腺癌和卵巢癌的风险分别是50%~85%和15%~45%,有BRCA2基因突变者,患乳腺癌和卵巢癌的风险分别是50%~85%和10%~20%。
通过对BRCA1/2的检测,可以反映乳腺癌的发生发展,也可筛检出乳腺癌、卵巢癌及其他相关恶性肿瘤的高危人群,利于该类疾病的早期诊断治疗。
目前,普遍应用的BRCA基因突变检测方法主要有以下几种:荧光定量PCR技术,该技术灵敏度高、特异性强、自动化程度高,但是会存在样品污染、假阳性高的情况,并且每次只能检测一种类型。限制小片段长度多态性分析法(RFLP发)用于检测酶切位点改变的基因,可直接判断基因型,但是不能用于没有产生新酶切位点的基因检测;此外,RFLP实验操作繁琐,检测周期长,成本高,假阳性,非闭管操作,易于污染,难以满足临床检测要求。DNA一代测序法,两端靠近引物的序列容易测不准,且测序周期较长,操作复杂,易于污染,成本昂贵,所以该方法很难满足实际应用的需要。
因此,急需能够相对方便、快捷、检测周期短、针对性强、检测结果准确可靠的检测手段。
发明内容
为达到上述目的,本发明提供一种BRCA基因热点SNP位点检测组合物,该组合物检测通量高且灵敏度特异性强,一次检测能够覆盖2000多个热点SNP位点。
本发明的技术方案是:BRCA基因易感SNP位点检测组合物,所述BRCA基因易感SNP位点检测组合物包括SEQNO:1~SEQNO:448的引物;
所述SEQNO:1~SEQNO:448的引物序列见表1。
优选的,所述BRCA基因易感SNP位点检测组合物的组成是:MasterMix11μl、包含所述SEQNO:1~SEQNO:448引物的引物panel5.5μl、待测DNA样品4.5μl。
所述SEQNO:1~SEQNO:448引物在引物panel的浓度均为100nM。
所述MasterMix组成为:PCRbuffer(5×)4μl、MgCl21.5μl、Taq酶1.5μl、ddH2O4μl。
优选的,所述BRCA基因易感SNP位点检测组合物的PCR反应条件为:92~97℃预变性3~10分钟,聚合酶链式反应扩增阶段:92~97℃变性10~20s,50~65℃退火10~30s,70~75℃延伸10~20s,并进行10~15个循环。
待测DNA样品采用多重PCR酶进行扩增后构建文库与上机质控品一起进行大规模平行测序(二代测序),仪器获得的结果经数据处理和生物信息学分析,得出样本中含有的SNP位点等信息。
所述质控品为加入的1%controlparticles。是一种商品化试剂,包含在上机测序的试剂盒PGMSequencingOT2kit中,作为上机测序实验的内参,对测序情况进行评估和质控,如果测序结果中不包含1%的controlparticles结果,说明上机实验失败,结果不可靠。
所述待测DNA样品为人类基因组DNA。
多重PCR过程同时进行阴性对照实验,所用阴性样本为正常人基因组DNA。
待测DNA样品为人类细胞DNA、肿瘤组织基因组DNA、外周血细胞DNA、体液DNA或排泄物细胞DNA。
本发明的检测基因为BRCA1、BRCA2基因,包括其全部外显子和部分内含子中热点SNP位点(见表2)。
本发明所称的BRCA基因包含BRCA1和BRCA2基因的所有外显子和部分内含子易感SNP位点,包括BRCA1基因位点chr17:41219666(rs80357862),BRCA2基因chr13:32888473(rs206115)等2007个易感SNP位点(表2)。
本发明组合物中的引物是针对BRCA1和BRCA2基因易感SNP位点可能的某一段序列进行设计。引物经优化设计和修饰后,偏向性扩增的程度降低,各引物之间相互干扰性小,特异性强,扩增效果好。这些引物以混合物形式溶解于一管中,在实验中同时加入。
测序反应体系的组成为:DNA模板多重PCR反应、模板文库构建、上机模板准备和富集反应、上机测序反应和测试数据处理分析。
上机模板准备和富集反应过程包括模板油包水扩增和阳性模板富集,所述两个过程中试剂组成包括IonPGMBeads、PGMTemplateOT2Solutions、1%controlparticle等、仪器组成主要包含IonOneTouch和IonOneTouchES。上机模板准备和上机过程中用到的试剂和耗材与IonTorrent二代测序平台相配套,包括PGMTemplateOT2kit、PGMSequencingOT2kit、Ion318chip等部分。上机反应获得的数据结果通过序列筛选、拼接和比对等方法以及生物信息学分析,最终获得测试样本的SNP位点信息。
上机测序反应过程包括PGM测序反应过程,其原理是利用半导体技术来检测合成过程中核苷酸掺入时释放的质子,以此测定DNA的碱基序列。
模板文库构建过程包括末端补平修复、末端连接测序接头、模板扩增和纯化,所述反应体系中包含0.2-1U末端补平酶、0.2-1U连接酶、0.2-1U扩增Taq酶、10-50mM测序接头A和P1、10-20mM测序接头A和P1通用引物、1-10×Buffer和0.2-1.8×Ampure纯化磁珠等试剂。
所述检测结果数据处理、生物信息学分析得出检测基因的特定SNP位点情况。
测试数据处理分析包括测序数据的转换、拼接、质控和突变位点分析等过程,通过数据的处理最终获得检测样本SNP位点的信息。
本发明具备检测通量高、灵敏度高、特异性高的特性,灵敏度可以达到0.01%,样本的DNA浓度可以低至0.1-1ng/μl。
SEQNO:1~SEQNO:448的引物序列如表1所示。
表1BRCA基因易感SNP位点检测引物序列
测试数据处理分析包括测序数据的转换、拼接、质控和突变位点分析等过程,通过数据的处理最终获得检测样本SNP位点的信息。
所述检测基因为BRCA1和BRCA2基因,本发明待检测易感SNP位点如下:
表2BRCA1和BRCA2基因易感SNP位点
Gene | Location | RS_ID | Gene | Location | RS_ID | Gene | Location | RS_ID |
BRCA1 | chr17:41245027 | rs1800709 | BRCA1 | chr17:41243954 | rs80357562 | BRCA2 | chr13:32914708 | rs80359567 |
BRCA1 | chr17:41215969 | rs1800747 | BRCA1 | chr17:41242984 | rs80357565 | BRCA2 | chr13:32914711 | rs80359568 |
BRCA1 | chr17:41244429 | rs4986852 | BRCA1 | chr17:41256181 | rs80357568 | BRCA2 | chr13:32914730 | rs80359569 |
BRCA1 | chr17:41258504 | rs28897672 | BRCA1 | chr17:41246224 | rs80357570 | BRCA2 | chr13:32914732 | rs80359570 |
BRCA1 | chr17:41243800 | rs28897686 | BRCA1 | chr17:41242980 | rs80357572 | BRCA2 | chr13:32914865 | rs80359577 |
BRCA1 | chr17:41215920 | rs28897696 | BRCA1 | chr17:41244150 | rs80357577 | BRCA2 | chr13:32914865 | rs80359578 |
BRCA1 | chr17:41245285 | rs41286296 | BRCA1 | chr17:41243778 | rs80357579 | BRCA2 | chr13:32890660 | rs80359582 |
BRCA1 | chr17:41234451 | rs41293455 | BRCA1 | chr17:41243706 | rs80357584 | BRCA2 | chr13:32914923 | rs80359587 |
BRCA1 | chr17:41215947 | rs41293459 | BRCA1 | chr17:41243918 | rs80357589 | BRCA2 | chr13:32914936 | rs80359590 |
BRCA1 | chr17:41215390 | rs41293461 | BRCA1 | chr17:41245470 | rs80357595 | BRCA2 | chr13:32914942 | rs80359595 |
BRCA1 | chr17:41203088 | rs41293463 | BRCA1 | chr17:41246207 | rs80357597 | BRCA2 | chr13:32914982 | rs80359599 |
BRCA1 | chr17:41197784 | rs41293465 | BRCA1 | chr17:41245294 | rs80357602 | BRCA2 | chr13:32915027 | rs80359601 |
BRCA1 | chr17:41209139 | rs45553935 | BRCA1 | chr17:41244943 | rs80357603 | BRCA2 | chr13:32915045 | rs80359603 |
BRCA1 | chr17:41245759 | rs55650082 | BRCA1 | chr17:41215940 | rs80357608 | BRCA2 | chr13:32915083 | rs80359606 |
BRCA1 | chr17:41215948 | rs55770810 | BRCA1 | chr17:41246567 | rs80357610 | BRCA2 | chr13:32915130 | rs80359612 |
BRCA1 | chr17:41258494 | rs55851803 | BRCA1 | chr17:41244627 | rs80357611 | BRCA2 | chr13:32915133 | rs80359613 |
BRCA1 | chr17:41245333 | rs56329598 | BRCA1 | chr17:41244539 | rs80357617 | BRCA2 | chr13:32915135 | rs80359614 |
BRCA1 | chr17:41246077 | rs62625303 | BRCA1 | chr17:41276040 | rs80357633 | BRCA2 | chr13:32915136 | rs80359615 |
BRCA1 | chr17:41245159 | rs62625306 | BRCA1 | chr17:41244319 | rs80357635 | BRCA2 | chr13:32915170 | rs80359620 |
BRCA1 | chr17:41243950 | rs62625307 | BRCA1 | chr17:41244862 | rs80357636 | BRCA2 | chr13:32915174 | rs80359621 |
BRCA1 | chr17:41243941 | rs62625308 | BRCA1 | chr17:41223181 | rs80357641 | BRCA2 | chr13:32915301 | rs80359625 |
BRCA1 | chr17:41246540 | rs67284603 | BRCA1 | chr17:41276048 | rs80357642 | BRCA2 | chr13:32920967 | rs80359628 |
BRCA1 | chr17:41219625 | rs80187739 | BRCA1 | chr17:41245587 | rs80357643 | BRCA2 | chr13:32905070 | rs80359630 |
BRCA1 | chr17:41244980 | rs80356832 | BRCA1 | chr17:41246625 | rs80357644 | BRCA2 | chr13:32905074 | rs80359633 |
BRCA1 | chr17:41209069 | rs80356854 | BRCA1 | chr17:41243786 | rs80357645 | BRCA2 | chr13:32929022 | rs80359635 |
BRCA1 | chr17:41242961 | rs80356857 | BRCA1 | chr17:41243646 | rs80357646 | BRCA2 | chr13:32929146 | rs80359639 |
BRCA1 | chr17:41215926 | rs80356860 | BRCA1 | chr17:41234582 | rs80357649 | BRCA2 | chr13:32929216 | rs80359643 |
BRCA1 | chr17:41223063 | rs80356862 | BRCA1 | chr17:41245337 | rs80357654 | BRCA2 | chr13:32929350 | rs80359646 |
BRCA1 | chr17:41258525 | rs80356864 | BRCA1 | chr17:41222986 | rs80357655 | BRCA2 | chr13:32930572 | rs80359652 |
BRCA1 | chr17:41243707 | rs80356866 | BRCA1 | chr17:41245264 | rs80357657 | BRCA2 | chr13:32905122 | rs80359654 |
BRCA1 | chr17:41199678 | rs80356868 | BRCA1 | chr17:41245136 | rs80357664 | BRCA2 | chr13:32930654 | rs80359656 |
BRCA1 | chr17:41244627 | rs80356872 | BRCA1 | chr17:41246446 | rs80357665 | BRCA2 | chr13:32930672 | rs80359657 |
BRCA1 | chr17:41197751 | rs80356873 | BRCA1 | chr17:41243841 | rs80357666 | BRCA2 | chr13:32930672 | rs80359658 |
BRCA1 | chr17:41245390 | rs80356875 | BRCA1 | chr17:41246652 | rs80357670 | BRCA2 | chr13:32930685 | rs80359660 |
BRCA1 | chr17:41219652 | rs80356879 | BRCA1 | chr17:41243631 | rs80357678 | BRCA2 | chr13:32905129 | rs80359661 |
BRCA1 | chr17:41226471 | rs80356881 | BRCA1 | chr17:41244259 | rs80357686 | BRCA2 | chr13:32930722 | rs80359665 |
BRCA1 | chr17:41226499 | rs80356885 | BRCA1 | chr17:41246594 | rs80357690 | BRCA2 | chr13:32931888 | rs80359668 |
BRCA1 | chr17:41256190 | rs80356888 | BRCA1 | chr17:41243023 | rs80357691 | BRCA2 | chr13:32931950 | rs80359674 |
BRCA1 | chr17:41245549 | rs80356889 | BRCA1 | chr17:41244676 | rs80357693 | BRCA2 | chr13:32931980 | rs80359676 |
BRCA1 | chr17:41246196 | rs80356891 | BRCA1 | chr17:41245158 | rs80357695 | BRCA2 | chr13:32932022 | rs80359678 |
BRCA1 | chr17:41245936 | rs80356893 | BRCA1 | chr17:41226427 | rs80357699 | BRCA2 | chr13:32932023 | rs80359679 |
BRCA1 | chr17:41215963 | rs80356896 | BRCA1 | chr17:41245142 | rs80357706 | BRCA2 | chr13:32932052 | rs80359681 |
BRCA1 | chr17:41245861 | rs80356898 | BRCA1 | chr17:41251853 | rs80357708 | BRCA2 | chr13:32936701 | rs80359685 |
BRCA1 | chr17:41243830 | rs80356903 | BRCA1 | chr17:41215951 | rs80357710 | BRCA2 | chr13:32936788 | rs80359688 |
BRCA1 | chr17:41245927 | rs80356904 | BRCA1 | chr17:41234492 | rs80357716 | BRCA2 | chr13:32936808 | rs80359689 |
BRCA1 | chr17:41245603 | rs80356907 | BRCA1 | chr17:41244840 | rs80357717 | BRCA2 | chr13:32937368 | rs80359691 |
BRCA1 | chr17:41246490 | rs80356908 | BRCA1 | chr17:41246696 | rs80357719 | BRCA2 | chr13:32937397 | rs80359692 |
BRCA1 | chr17:41258473 | rs80356913 | BRCA1 | chr17:41246749 | rs80357724 | BRCA2 | chr13:32937406 | rs80359693 |
BRCA1 | chr17:41197776 | rs80356914 | BRCA1 | chr17:41246645 | rs80357726 | BRCA2 | chr13:32937426 | rs80359695 |
BRCA1 | chr17:41246215 | rs80356915 | BRCA1 | chr17:41243506 | rs80357727 | BRCA2 | chr13:32937469 | rs80359696 |
BRCA1 | chr17:41243908 | rs80356923 | BRCA1 | chr17:41267793 | rs80357728 | BRCA2 | chr13:32937558 | rs80359697 |
BRCA1 | chr17:41244945 | rs80356925 | BRCA1 | chr17:41215365 | rs80357730 | BRCA2 | chr13:32937592 | rs80359704 |
BRCA1 | chr17:41245801 | rs80356928 | BRCA1 | chr17:41256895 | rs80357738 | BRCA2 | chr13:32937636 | rs80359705 |
BRCA1 | chr17:41276061 | rs80356929 | BRCA1 | chr17:41242963 | rs80357742 | BRCA2 | chr13:32937661 | rs80359706 |
BRCA1 | chr17:41228617 | rs80356932 | BRCA1 | chr17:41246850 | rs80357747 | BRCA2 | chr13:32944550 | rs80359708 |
BRCA1 | chr17:41246489 | rs80356935 | BRCA1 | chr17:41256250 | rs80357754 | BRCA2 | chr13:32944602 | rs80359709 |
BRCA1 | chr17:41256277 | rs80356936 | BRCA1 | chr17:41197807 | rs80357757 | BRCA2 | chr13:32944643 | rs80359710 |
BRCA1 | chr17:41197781 | rs80356942 | BRCA1 | chr17:41246653 | rs80357759 | BRCA2 | chr13:32944681 | rs80359711 |
BRCA1 | chr17:41245210 | rs80356945 | BRCA1 | chr17:41215958 | rs80357760 | BRCA2 | chr13:32945106 | rs80359712 |
BRCA1 | chr17:41251825 | rs80356947 | BRCA1 | chr17:41244291 | rs80357764 | BRCA2 | chr13:32945110 | rs80359713 |
BRCA1 | chr17:41245678 | rs80356950 | BRCA1 | chr17:41245654 | rs80357768 | BRCA2 | chr13:32945165 | rs80359717 |
BRCA1 | chr17:41245003 | rs80356951 | BRCA1 | chr17:41244389 | rs80357769 | BRCA2 | chr13:32945180 | rs80359718 |
BRCA1 | chr17:41245918 | rs80356952 | BRCA1 | chr17:41246566 | rs80357772 | BRCA2 | chr13:32945190 | rs80359720 |
BRCA1 | chr17:41226536 | rs80356953 | BRCA1 | chr17:41245468 | rs80357773 | BRCA2 | chr13:32945199 | rs80359721 |
BRCA1 | chr17:41197778 | rs80356959 | BRCA1 | chr17:41246563 | rs80357775 | BRCA2 | chr13:32950810 | rs80359723 |
BRCA1 | chr17:41199683 | rs80356962 | BRCA1 | chr17:41246107 | rs80357778 | BRCA2 | chr13:32950850 | rs80359725 |
BRCA1 | chr17:41201191 | rs80356969 | BRCA1 | chr17:41245251 | rs80357780 | BRCA2 | chr13:32953455 | rs80359728 |
BRCA1 | chr17:41244150 | rs80356971 | BRCA1 | chr17:41243025 | rs80357787 | BRCA2 | chr13:32953488 | rs80359729 |
BRCA1 | chr17:41244679 | rs80356973 | BRCA1 | chr17:41246750 | rs80357789 | BRCA2 | chr13:32953603 | rs80359730 |
BRCA1 | chr17:41215934 | rs80356974 | BRCA1 | chr17:41246705 | rs80357792 | BRCA2 | chr13:32953611 | rs80359731 |
BRCA1 | chr17:41197752 | rs80356977 | BRCA1 | chr17:41223166 | rs80357795 | BRCA2 | chr13:32953639 | rs80359732 |
BRCA1 | chr17:41244826 | rs80356978 | BRCA1 | chr17:41243876 | rs80357797 | BRCA2 | chr13:32953645 | rs80359733 |
BRCA1 | chr17:41245138 | rs80356982 | BRCA1 | chr17:41245070 | rs80357800 | BRCA2 | chr13:32906516 | rs80359738 |
BRCA1 | chr17:41245972 | rs80356984 | BRCA1 | chr17:41243029 | rs80357804 | BRCA2 | chr13:32953960 | rs80359742 |
BRCA1 | chr17:41226348 | rs80356988 | BRCA1 | chr17:41243905 | rs80357805 | BRCA2 | chr13:32953990 | rs80359744 |
BRCA1 | chr17:41234556 | rs80356989 | BRCA1 | chr17:41246652 | rs80357806 | BRCA2 | chr13:32954031 | rs80359747 |
BRCA1 | chr17:41256153 | rs80356991 | BRCA1 | chr17:41243776 | rs80357810 | BRCA2 | chr13:32954183 | rs80359750 |
BRCA1 | chr17:41226411 | rs80356992 | BRCA1 | chr17:41276081 | rs80357811 | BRCA2 | chr13:32954203 | rs80359751 |
BRCA1 | chr17:41228600 | rs80356997 | BRCA1 | chr17:41226448 | rs80357813 | BRCA2 | chr13:32954279 | rs80359752 |
BRCA1 | chr17:41245273 | rs80356999 | BRCA1 | chr17:41245437 | rs80357814 | BRCA2 | chr13:32968838 | rs80359753 |
BRCA1 | chr17:41244957 | rs80357003 | BRCA1 | chr17:41203091 | rs80357818 | BRCA2 | chr13:32968929 | rs80359757 |
BRCA1 | chr17:41244499 | rs80357004 | BRCA1 | chr17:41226428 | rs80357826 | BRCA2 | chr13:32968970 | rs80359759 |
BRCA1 | chr17:41245636 | rs80357005 | BRCA1 | chr17:41244172 | rs80357828 | BRCA2 | chr13:32968972 | rs80359760 |
BRCA1 | chr17:41244291 | rs80357006 | BRCA1 | chr17:41244558 | rs80357829 | BRCA2 | chr13:32968977 | rs80359761 |
BRCA1 | chr17:41246785 | rs80357009 | BRCA1 | chr17:41243898 | rs80357831 | BRCA2 | chr13:32969035 | rs80359766 |
BRCA1 | chr17:41246068 | rs80357010 | BRCA1 | chr17:41222997 | rs80357833 | BRCA2 | chr13:32971040 | rs80359767 |
BRCA1 | chr17:41234592 | rs80357011 | BRCA1 | chr17:41245818 | rs80357834 | BRCA2 | chr13:32906571 | rs80359770 |
BRCA1 | chr17:41244148 | rs80357018 | BRCA1 | chr17:41223176 | rs80357837 | BRCA2 | chr13:32972316 | rs80359772 |
BRCA1 | chr17:41243533 | rs80357021 | BRCA1 | chr17:41244188 | rs80357843 | BRCA2 | chr13:32972322 | rs80359773 |
BRCA1 | chr17:41244838 | rs80357035 | BRCA1 | chr17:41243978 | rs80357845 | BRCA2 | chr13:32972326 | rs80359774 |
BRCA1 | chr17:41243653 | rs80357038 | BRCA1 | chr17:41242978 | rs80357847 | BRCA2 | chr13:32972518 | rs80359776 |
BRCA1 | chr17:41201157 | rs80357055 | BRCA1 | chr17:41243769 | rs80357849 | BRCA2 | chr13:32906609 | rs80359778 |
BRCA1 | chr17:41245360 | rs80357058 | BRCA1 | chr17:41209116 | rs80357852 | BRCA2 | chr13:32950928 | rs80359803 |
BRCA1 | chr17:41219633 | rs80357061 | BRCA1 | chr17:41228506 | rs80357854 | BRCA2 | chr13:32969070 | rs80359808 |
BRCA1 | chr17:41245239 | rs80357063 | BRCA1 | chr17:41244495 | rs80357856 | BRCA2 | chr13:32890665 | rs81002796 |
BRCA1 | chr17:41258495 | rs80357064 | BRCA1 | chr17:41245422 | rs80357871 | BRCA2 | chr13:32900288 | rs81002797 |
BRCA1 | chr17:41201185 | rs80357065 | BRCA1 | chr17:41256237 | rs80357881 | BRCA2 | chr13:32944695 | rs81002798 |
BRCA1 | chr17:41234439 | rs80357067 | BRCA1 | chr17:41251882 | rs80357882 | BRCA2 | chr13:32954051 | rs81002802 |
BRCA1 | chr17:41246355 | rs80357068 | BRCA1 | chr17:41244353 | rs80357883 | BRCA2 | chr13:32893464 | rs81002805 |
BRCA1 | chr17:41201181 | rs80357069 | BRCA1 | chr17:41251868 | rs80357887 | BRCA2 | chr13:32932067 | rs81002809 |
BRCA1 | chr17:41242998 | rs80357071 | BRCA1 | chr17:41244658 | rs80357890 | BRCA2 | chr13:32953453 | rs81002812 |
BRCA1 | chr17:41245513 | rs80357082 | BRCA1 | chr17:41244182 | rs80357892 | BRCA2 | chr13:32950933 | rs81002813 |
BRCA1 | chr17:41246296 | rs80357083 | BRCA1 | chr17:41215386 | rs80357895 | BRCA2 | chr13:32903579 | rs81002820 |
BRCA1 | chr17:41258497 | rs80357086 | BRCA1 | chr17:41246461 | rs80357897 | BRCA2 | chr13:32928996 | rs81002823 |
BRCA1 | chr17:41244217 | rs80357089 | BRCA1 | chr17:41244847 | rs80357899 | BRCA2 | chr13:32905055 | rs81002831 |
BRCA1 | chr17:41258503 | rs80357093 | BRCA1 | chr17:41276045 | rs80357914 | BRCA2 | chr13:32936658 | rs81002836 |
BRCA1 | chr17:41244124 | rs80357101 | BRCA1 | chr17:41226411 | rs80357915 | BRCA2 | chr13:32937671 | rs81002837 |
BRCA1 | chr17:41215378 | rs80357104 | BRCA1 | chr17:41243678 | rs80357918 | BRCA2 | chr13:32893467 | rs81002840 |
BRCA1 | chr17:41244229 | rs80357106 | BRCA1 | chr17:41243017 | rs80357921 | BRCA2 | chr13:32930748 | rs81002843 |
BRCA1 | chr17:41276112 | rs80357111 | BRCA1 | chr17:41243786 | rs80357928 | BRCA2 | chr13:32953884 | rs81002844 |
BRCA1 | chr17:41244614 | rs80357115 | BRCA1 | chr17:41245332 | rs80357930 | BRCA2 | chr13:32905168 | rs81002846 |
BRCA1 | chr17:41245755 | rs80357118 | BRCA1 | chr17:41243034 | rs80357935 | BRCA2 | chr13:32900635 | rs81002849 |
BRCA1 | chr17:41209095 | rs80357123 | BRCA1 | chr17:41245509 | rs80357940 | BRCA2 | chr13:32900377 | rs81002853 |
BRCA1 | chr17:41228619 | rs80357130 | BRCA1 | chr17:41244189 | rs80357945 | BRCA2 | chr13:32900634 | rs81002858 |
BRCA1 | chr17:41244985 | rs80357131 | BRCA1 | chr17:41244935 | rs80357948 | BRCA2 | chr13:32936659 | rs81002860 |
BRCA1 | chr17:41251834 | rs80357133 | BRCA1 | chr17:41267764 | rs80357949 | BRCA2 | chr13:32954142 | rs81002862 |
BRCA1 | chr17:41276080 | rs80357134 | BRCA1 | chr17:41246753 | rs80357955 | BRCA2 | chr13:32920962 | rs81002863 |
BRCA1 | chr17:41244145 | rs80357136 | BRCA1 | chr17:41243999 | rs80357956 | BRCA2 | chr13:32971033 | rs81002868 |
BRCA1 | chr17:41246446 | rs80357139 | BRCA1 | chr17:41244936 | rs80357962 | BRCA2 | chr13:32936831 | rs81002873 |
BRCA1 | chr17:41244309 | rs80357145 | BRCA1 | chr17:41244447 | rs80357967 | BRCA2 | chr13:32937315 | rs81002874 |
BRCA1 | chr17:41228509 | rs80357148 | BRCA1 | chr17:41244986 | rs80357968 | BRCA2 | chr13:32953653 | rs81002882 |
BRCA1 | chr17:41244436 | rs80357161 | BRCA1 | chr17:41246187 | rs80357969 | BRCA2 | chr13:32954283 | rs81002883 |
BRCA1 | chr17:41243859 | rs80357162 | BRCA1 | chr17:41244866 | rs80357971 | BRCA2 | chr13:32890666 | rs81002885 |
BRCA1 | chr17:41267762 | rs80357164 | BRCA1 | chr17:41267759 | rs80357972 | BRCA2 | chr13:32950805 | rs81002886 |
BRCA1 | chr17:41244528 | rs80357168 | BRCA1 | chr17:41234526 | rs80357977 | BRCA2 | chr13:32968825 | rs81002889 |
BRCA1 | chr17:41244871 | rs80357170 | BRCA1 | chr17:41246212 | rs80357978 | BRCA2 | chr13:32950932 | rs81002893 |
BRCA1 | chr17:41243491 | rs80357178 | BRCA1 | chr17:41244707 | rs80357984 | BRCA2 | chr13:32972297 | rs81002895 |
BRCA1 | chr17:41245111 | rs80357186 | BRCA1 | chr17:41243787 | rs80357986 | BRCA2 | chr13:32900751 | rs81002897 |
BRCA1 | chr17:41243494 | rs80357202 | BRCA1 | chr17:41244255 | rs80357992 | BRCA2 | chr13:32900752 | rs81002899 |
BRCA1 | chr17:41219700 | rs80357204 | BRCA1 | chr17:41243777 | rs80357993 | BRCA2 | chr13:32936719 | rs142899125 |
BRCA1 | chr17:41256189 | rs80357207 | BRCA1 | chr17:41244217 | rs80357996 | BRCA2 | chr13:32915246 | rs180670511 |
BRCA1 | chr17:41243731 | rs80357208 | BRCA1 | chr17:41245146 | rs80357999 | BRCA2 | chr13:32913572 | rs200265692 |
BRCA1 | chr17:41246599 | rs80357211 | BRCA1 | chr17:41246158 | rs273897659 | BRCA2 | chr13:32907223 | rs276174811 |
BRCA1 | chr17:41246482 | rs80357215 | BRCA1 | chr17:41245986 | rs273897663 | BRCA2 | chr13:32907469 | rs276174815 |
BRCA1 | chr17:41201199 | rs80357219 | BRCA1 | chr17:41245477 | rs273898676 | BRCA2 | chr13:32910667 | rs276174819 |
BRCA1 | chr17:41245729 | rs80357220 | BRCA1 | chr17:41244735 | rs273899689 | BRCA2 | chr13:32910931 | rs276174822 |
BRCA1 | chr17:41215900 | rs80357222 | BRCA1 | chr17:41244552 | rs273899692 | BRCA2 | chr13:32911095 | rs276174824 |
BRCA1 | chr17:41244748 | rs80357223 | BRCA1 | chr17:41256882 | rs273899694 | BRCA2 | chr13:32911769 | rs276174833 |
BRCA1 | chr17:41226414 | rs80357229 | BRCA1 | chr17:41244359 | rs273899701 | BRCA2 | chr13:32912431 | rs276174838 |
BRCA1 | chr17:41245410 | rs80357233 | BRCA1 | chr17:41243998 | rs273899709 | BRCA2 | chr13:32900291 | rs276174848 |
BRCA1 | chr17:41256966 | rs80357234 | BRCA1 | chr17:41243510 | rs273900721 | BRCA2 | chr13:32900658 | rs276174857 |
BRCA1 | chr17:41215389 | rs80357239 | BRCA1 | chr17:41276045 | rs386833395 | BRCA2 | chr13:32914382 | rs276174864 |
BRCA1 | chr17:41226402 | rs80357248 | BRCA1 | chr17:41246723 | rs387906563 | BRCA2 | chr13:32914459 | rs276174865 |
BRCA1 | chr17:41244913 | rs80357251 | BRCA1 | chr17:41245333 | rs397507197 | BRCA2 | chr13:32914986 | rs276174874 |
BRCA1 | chr17:41243680 | rs80357254 | BRCA1 | chr17:41244683 | rs397507205 | BRCA2 | chr13:32915165 | rs276174875 |
BRCA1 | chr17:41243029 | rs80357259 | BRCA1 | chr17:41244566 | rs397507207 | BRCA2 | chr13:32915207 | rs276174876 |
BRCA1 | chr17:41242963 | rs80357260 | BRCA1 | chr17:41244510 | rs397507208 | BRCA2 | chr13:32929123 | rs276174889 |
BRCA1 | chr17:41243581 | rs80357262 | BRCA1 | chr17:41243776 | rs397507218 | BRCA2 | chr13:32936717 | rs276174896 |
BRCA1 | chr17:41245632 | rs80357267 | BRCA1 | chr17:41243695 | rs397507221 | BRCA2 | chr13:32937341 | rs276174900 |
BRCA1 | chr17:41197790 | rs80357268 | BRCA1 | chr17:41245030 | rs397508974 | BRCA2 | chr13:32906424 | rs276174902 |
BRCA1 | chr17:41243763 | rs80357269 | BRCA1 | chr17:41244803 | rs397509007 | BRCA2 | chr13:32937573 | rs276174903 |
BRCA1 | chr17:41226405 | rs80357277 | BRCA1 | chr17:41244711 | rs397509016 | BRCA2 | chr13:32937662 | rs276174904 |
BRCA1 | chr17:41244208 | rs80357278 | BRCA1 | chr17:41234439 | rs397509164 | BRCA2 | chr13:32950821 | rs276174910 |
BRCA1 | chr17:41246149 | rs80357279 | BRCA1 | chr17:41246588 | rs397509339 | BRCA2 | chr13:32953547 | rs276174912 |
BRCA1 | chr17:41245708 | rs80357282 | BRCA1 | chr17:41246170 | rs398122633 | BRCA2 | chr13:32953568 | rs276174913 |
BRCA1 | chr17:41201198 | rs80357284 | BRCA1 | chr17:41276095 | rs398122648 | BRCA2 | chr13:32914347 | rs375064902 |
BRCA1 | chr17:41276113 | rs80357287 | BRCA1 | chr17:41258481 | rs398122651 | BRCA2 | chr13:32914453 | rs387907575 |
BRCA1 | chr17:41215370 | rs80357291 | BRCA1 | chr17:41245416 | rs398122653 | BRCA2 | chr13:32906771 | rs397507262 |
BRCA1 | chr17:41246586 | rs80357292 | BRCA1 | chr17:41245301 | rs398122654 | BRCA2 | chr13:32906820 | rs397507265 |
BRCA1 | chr17:41244684 | rs80357295 | BRCA1 | chr17:41244645 | rs398122670 | BRCA2 | chr13:32906868 | rs397507266 |
BRCA1 | chr17:41244004 | rs80357296 | BRCA1 | chr17:41243948 | rs398122674 | BRCA2 | chr13:32907208 | rs397507272 |
BRCA1 | chr17:41245443 | rs80357298 | BRCA1 | chr17:41243029 | rs398122682 | BRCA2 | chr13:32907320 | rs397507274 |
BRCA1 | chr17:41223130 | rs80357303 | BRCA1 | chr17:41246399 | rs431825384 | BRCA2 | chr13:32907414 | rs397507276 |
BRCA1 | chr17:41246098 | rs80357304 | BRCA1 | chr17:41245968 | rs431825387 | BRCA2 | chr13:32907465 | rs397507278 |
BRCA1 | chr17:41234520 | rs80357305 | BRCA1 | chr17:41245446 | rs431825389 | BRCA2 | chr13:32910462 | rs397507279 |
BRCA1 | chr17:41197777 | rs80357307 | BRCA1 | chr17:41245215 | rs431825390 | BRCA2 | chr13:32910723 | rs397507282 |
BRCA1 | chr17:41243887 | rs80357310 | BRCA1 | chr17:41209077 | rs431825414 | BRCA2 | chr13:32910816 | rs397507284 |
BRCA1 | chr17:41244239 | rs80357317 | BRCA1 | chr17:41245043 | rs483353078 | BRCA2 | chr13:32910918 | rs397507285 |
BRCA1 | chr17:41243611 | rs80357318 | BRCA1 | chr17:41242990 | rs483353079 | BRCA2 | chr13:32910972 | rs397507286 |
BRCA1 | chr17:41246765 | rs80357321 | BRCA1 | chr17:41246249 | rs483353083 | BRCA2 | chr13:32911410 | rs397507296 |
BRCA1 | chr17:41246726 | rs80357331 | BRCA1 | chr17:41228538 | rs483353084 | BRCA2 | chr13:32893463 | rs397507303 |
BRCA1 | chr17:41197728 | rs80357336 | BRCA1 | chr17:41244259 | rs483353088 | BRCA2 | chr13:32911674 | rs397507304 |
BRCA1 | chr17:41246503 | rs80357338 | BRCA1 | chr17:41243976 | rs483353089 | BRCA2 | chr13:32911800 | rs397507305 |
BRCA1 | chr17:41243584 | rs80357343 | BRCA1 | chr17:41256279 | rs483353093 | BRCA2 | chr13:32912340 | rs397507317 |
BRCA1 | chr17:41246256 | rs80357346 | BRCA1 | chr17:41226378 | rs483353094 | BRCA2 | chr13:32899285 | rs397507318 |
BRCA1 | chr17:41215364 | rs80357347 | BRCA1 | chr17:41223234 | rs483353095 | BRCA2 | chr13:32899292 | rs397507320 |
BRCA1 | chr17:41223253 | rs80357349 | BRCA1 | chr17:41219691 | rs483353097 | BRCA2 | chr13:32912505 | rs397507321 |
BRCA1 | chr17:41256945 | rs80357350 | BRCA1 | chr17:41219665 | rs483353098 | BRCA2 | chr13:32912643 | rs397507325 |
BRCA1 | chr17:41223121 | rs80357352 | BRCA1 | chr17:41247907 | rs483353106 | BRCA2 | chr13:32912735 | rs397507327 |
BRCA1 | chr17:41245588 | rs80357355 | BRCA1 | chr17:41246740 | rs483353107 | BRCA2 | chr13:32912962 | rs397507334 |
BRCA1 | chr17:41243884 | rs80357356 | BRCA1 | chr17:41246714 | rs483353108 | BRCA2 | chr13:32900378 | rs397507340 |
BRCA1 | chr17:41226420 | rs80357366 | BRCA1 | chr17:41246696 | rs483353109 | BRCA2 | chr13:32913492 | rs397507346 |
BRCA1 | chr17:41209107 | rs80357367 | BRCA1 | chr17:41256912 | rs587776485 | BRCA2 | chr13:32913928 | rs397507351 |
BRCA1 | chr17:41244118 | rs80357369 | BRCA1 | chr17:41244900 | rs80357513 | BRCA2 | chr13:32913990 | rs397507353 |
BRCA1 | chr17:41256165 | rs80357372 | BRCA1 | chr17:41219635 | rs80358344 | BRCA2 | chr13:32914069 | rs397507355 |
BRCA1 | chr17:41244787 | rs80357377 | BRCA1 | chr17:41246425 | rs273897652 | BRCA2 | chr13:32914123 | rs397507357 |
BRCA1 | chr17:41245145 | rs80357381 | BRCA1 | chr17:41244069 | rs273899707 | BRCA2 | chr13:32915058 | rs397507373 |
BRCA1 | chr17:41258474 | rs80357382 | BRCA1 | chr17:41243831 | rs273900714 | BRCA2 | chr13:32929225 | rs397507384 |
BRCA1 | chr17:41246407 | rs80357385 | BRCA1 | chr17:41228596 | rs273900730 | BRCA2 | chr13:32929248 | rs397507385 |
BRCA1 | chr17:41228505 | rs80357389 | BRCA1 | chr17:41244712 | rs386134270 | BRCA2 | chr13:32931878 | rs397507389 |
BRCA1 | chr17:41245531 | rs80357391 | BRCA1 | chr17:41246624 | rs397509335 | BRCA2 | chr13:32936817 | rs397507395 |
BRCA1 | chr17:41246748 | rs80357392 | BRCA1 | chr17:41243480 | rs80357508 | BRCA2 | chr13:32945092 | rs397507404 |
BRCA1 | chr17:41243023 | rs80357397 | BRCA1 | chr17:41244870 | rs80357518 | BRCA2 | chr13:32950851 | rs397507409 |
BRCA1 | chr17:41222950 | rs80357401 | BRCA1 | chr17:41245592 | rs80357526 | BRCA2 | chr13:32950854 | rs397507410 |
BRCA1 | chr17:41244280 | rs80357402 | BRCA1 | chr17:41276074 | rs80357530 | BRCA2 | chr13:32950869 | rs397507411 |
BRCA1 | chr17:41244159 | rs80357405 | BRCA1 | chr17:41242980 | rs80357532 | BRCA2 | chr13:32950930 | rs397507412 |
BRCA1 | chr17:41246282 | rs80357417 | BRCA1 | chr17:41242976 | rs80357538 | BRCA2 | chr13:32954030 | rs397507419 |
BRCA1 | chr17:41215907 | rs80357418 | BRCA1 | chr17:41226365 | rs80357561 | BRCA2 | chr13:32954030 | rs397507420 |
BRCA1 | chr17:41244808 | rs80357419 | BRCA1 | chr17:41245664 | rs80357567 | BRCA2 | chr13:32954261 | rs397507422 |
BRCA1 | chr17:41244209 | rs80357421 | BRCA1 | chr17:41244219 | rs80357575 | BRCA2 | chr13:32968843 | rs397507424 |
BRCA1 | chr17:41244370 | rs80357424 | BRCA1 | chr17:41219669 | rs80357580 | BRCA2 | chr13:32971056 | rs397507430 |
BRCA1 | chr17:41245354 | rs80357426 | BRCA1 | chr17:41245724 | rs80357585 | BRCA2 | chr13:32906613 | rs397507437 |
BRCA1 | chr17:41246019 | rs80357427 | BRCA1 | chr17:41244866 | rs80357596 | BRCA2 | chr13:32907114 | rs397507591 |
BRCA1 | chr17:41209086 | rs80357432 | BRCA1 | chr17:41244818 | rs80357605 | BRCA2 | chr13:32911104 | rs397507634 |
BRCA1 | chr17:41223242 | rs80357433 | BRCA1 | chr17:41246048 | rs80357632 | BRCA2 | chr13:32893435 | rs397507646 |
BRCA1 | chr17:41226515 | rs80357437 | BRCA1 | chr17:41244778 | rs80357661 | BRCA2 | chr13:32911694 | rs397507658 |
BRCA1 | chr17:41243655 | rs80357440 | BRCA1 | chr17:41243869 | rs80357671 | BRCA2 | chr13:32911788 | rs397507663 |
BRCA1 | chr17:41267792 | rs80357443 | BRCA1 | chr17:41245139 | rs80357674 | BRCA2 | chr13:32911873 | rs397507666 |
BRCA1 | chr17:41245217 | rs80357444 | BRCA1 | chr17:41256959 | rs80357697 | BRCA2 | chr13:32913085 | rs397507732 |
BRCA1 | chr17:41267746 | rs80357446 | BRCA1 | chr17:41245937 | rs80357698 | BRCA2 | chr13:32914118 | rs397507793 |
BRCA1 | chr17:41245255 | rs80357449 | BRCA1 | chr17:41244216 | rs80357701 | BRCA2 | chr13:32914571 | rs397507826 |
BRCA1 | chr17:41209133 | rs80357450 | BRCA1 | chr17:41246754 | rs80357707 | BRCA2 | chr13:32914694 | rs397507833 |
BRCA1 | chr17:41243929 | rs80357455 | BRCA1 | chr17:41244826 | rs80357731 | BRCA2 | chr13:32915039 | rs397507866 |
BRCA1 | chr17:41243473 | rs80357456 | BRCA1 | chr17:41244527 | rs80357749 | BRCA2 | chr13:32929100 | rs397507897 |
BRCA1 | chr17:41244716 | rs80357458 | BRCA1 | chr17:41244225 | rs80357763 | BRCA2 | chr13:32930747 | rs397507922 |
BRCA1 | chr17:41243644 | rs80357461 | BRCA1 | chr17:41244217 | rs80357777 | BRCA2 | chr13:32931941 | rs397507932 |
BRCA1 | chr17:41203115 | rs80357463 | BRCA1 | chr17:41244068 | rs80357781 | BRCA2 | chr13:32937362 | rs397507954 |
BRCA1 | chr17:41246432 | rs80357468 | BRCA1 | chr17:41246101 | rs80357801 | BRCA2 | chr13:32945238 | rs397507997 |
BRCA1 | chr17:41258507 | rs80357471 | BRCA1 | chr17:41244781 | rs80357822 | BRCA2 | chr13:32950931 | rs397508007 |
BRCA1 | chr17:41246494 | rs80357472 | BRCA1 | chr17:41244739 | rs80357832 | BRCA2 | chr13:32906495 | rs397508009 |
BRCA1 | chr17:41276111 | rs80357475 | BRCA1 | chr17:41244749 | rs80357840 | BRCA2 | chr13:32954042 | rs397508037 |
BRCA1 | chr17:41199674 | rs80357477 | BRCA1 | chr17:41243689 | rs80357842 | BRCA2 | chr13:32968900 | rs397508047 |
BRCA1 | chr17:41246334 | rs80357481 | BRCA1 | chr17:41219666 | rs80357862 | BRCA2 | chr13:32913844 | rs398122531 |
BRCA1 | chr17:41244262 | rs80357485 | BRCA1 | chr17:41243614 | rs80357864 | BRCA2 | chr13:32914184 | rs398122539 |
BRCA1 | chr17:41246127 | rs80357490 | BRCA1 | chr17:41215367 | rs80357867 | BRCA2 | chr13:32914334 | rs398122541 |
BRCA1 | chr17:41209137 | rs80357496 | BRCA1 | chr17:41243789 | rs80357868 | BRCA2 | chr13:32914936 | rs398122557 |
BRCA1 | chr17:41244625 | rs80357497 | BRCA1 | chr17:41243687 | rs80357889 | BRCA2 | chr13:32914979 | rs398122559 |
BRCA1 | chr17:41267761 | rs80357498 | BRCA1 | chr17:41244869 | rs80357891 | BRCA2 | chr13:32915078 | rs398122561 |
BRCA1 | chr17:41244568 | rs80357502 | BRCA1 | chr17:41244214 | rs80357903 | BRCA2 | chr13:32903630 | rs398122565 |
BRCA1 | chr17:41245110 | rs80357503 | BRCA1 | chr17:41244820 | rs80357917 | BRCA2 | chr13:32929132 | rs398122576 |
BRCA1 | chr17:41243616 | rs80357504 | BRCA1 | chr17:41246702 | rs80357919 | BRCA2 | chr13:32937647 | rs398122601 |
BRCA1 | chr17:41246109 | rs80357505 | BRCA1 | chr17:41219668 | rs80357924 | BRCA2 | chr13:32937672 | rs398122602 |
BRCA1 | chr17:41246040 | rs80357506 | BRCA1 | chr17:41245722 | rs80357952 | BRCA2 | chr13:32944581 | rs398122605 |
BRCA1 | chr17:41244063 | rs80357509 | BRCA1 | chr17:41243790 | rs80357963 | BRCA2 | chr13:32945186 | rs398122608 |
BRCA1 | chr17:41244355 | rs80357511 | BRCA1 | chr17:41215363 | rs80357975 | BRCA2 | chr13:32953993 | rs398122609 |
BRCA1 | chr17:41243926 | rs80357512 | BRCA1 | chr17:41244529 | rs80357994 | BRCA2 | chr13:32954153 | rs398122610 |
BRCA1 | chr17:41246307 | rs80357514 | BRCA1 | chr17:41244431 | rs273899700 | BRCA2 | chr13:32968945 | rs398122612 |
BRCA1 | chr17:41244295 | rs80357517 | BRCA1 | chr17:41246158 | rs397508866 | BRCA2 | chr13:32971106 | rs398122617 |
BRCA1 | chr17:41244713 | rs80357519 | BRCA1 | chr17:41244203 | rs397509058 | BRCA2 | chr13:32972332 | rs398122618 |
BRCA1 | chr17:41245547 | rs80357521 | BRCA1 | chr17:41244109 | rs397509067 | BRCA2 | chr13:32972458 | rs398122622 |
BRCA1 | chr17:41245587 | rs80357522 | BRCA1 | chr17:41243483 | rs398122679 | BRCA2 | chr13:32972474 | rs398122623 |
BRCA1 | chr17:41246713 | rs80357523 | BRCA1 | chr17:41197590 | rs431825382 | BRCA2 | chr13:32950806 | rs398122711 |
BRCA1 | chr17:41245115 | rs80357524 | BRCA1 | chr17:41243507 | rs431825404 | BRCA2 | chr13:32953538 | rs398122715 |
BRCA1 | chr17:41246056 | rs80357527 | BRCA1 | chr17:41226433 | rs431825409 | BRCA2 | chr13:32907257 | rs398122729 |
BRCA1 | chr17:41246256 | rs80357528 | BRCA1 | chr17:41245351 | rs80357507 | BRCA2 | chr13:32893332 | rs398122733 |
BRCA1 | chr17:41243962 | rs80357531 | BRCA1 | chr17:41245347 | rs80357539 | BRCA2 | chr13:32910437 | rs398122735 |
BRCA1 | chr17:41244262 | rs80357533 | BRCA1 | chr17:41246595 | rs80357555 | BRCA2 | chr13:32910517 | rs398122737 |
BRCA1 | chr17:41246293 | rs80357535 | BRCA1 | chr17:41243677 | rs80357560 | BRCA2 | chr13:32893363 | rs398122741 |
BRCA1 | chr17:41247865 | rs80357537 | BRCA1 | chr17:41243844 | rs80357609 | BRCA2 | chr13:32910706 | rs398122742 |
BRCA1 | chr17:41256259 | rs80357544 | BRCA1 | chr17:41219660 | rs80357623 | BRCA2 | chr13:32910860 | rs398122746 |
BRCA1 | chr17:41243766 | rs80357545 | BRCA1 | chr17:41245831 | rs80357640 | BRCA2 | chr13:32910862 | rs398122747 |
BRCA1 | chr17:41234430 | rs80357548 | BRCA1 | chr17:41244219 | rs80357680 | BRCA2 | chr13:32911109 | rs398122748 |
BRCA1 | chr17:41244857 | rs80357549 | BRCA1 | chr17:41244820 | rs80357712 | BRCA2 | chr13:32911110 | rs398122749 |
BRCA1 | chr17:41251846 | rs80357551 | BRCA1 | chr17:41223215 | rs80357718 | BRCA2 | chr13:32911300 | rs398122753 |
BRCA1 | chr17:41215937 | rs80357553 | BRCA1 | chr17:41245350 | rs80357755 | BRCA2 | chr13:32911818 | rs398122762 |
BRCA1 | chr17:41245474 | rs80357554 | BRCA1 | chr17:41245349 | rs80357771 | BRCA2 | chr13:32911828 | rs398122763 |
BRCA1 | chr17:41234489 | rs80357556 | BRCA1 | chr17:41244681 | rs80357819 | BRCA2 | chr13:32912200 | rs398122769 |
BRCA1 | chr17:41199710 | rs80357558 | BRCA1 | chr17:41246040 | rs80357888 | BRCA2 | chr13:32912365 | rs398122772 |
BRCA1 | chr17:41244661 | rs80357559 | BRCA1 | chr17:41244678 | rs80357961 | BRCA2 | chr13:32912703 | rs398122777 |
BRCA1 | chr17:41243838 | rs80357564 | BRCA1 | chr17:41243705 | rs273900717 | BRCA2 | chr13:32900236 | rs398122779 |
BRCA1 | chr17:41245360 | rs80357566 | BRCA1 | chr17:41223152 | rs397507237 | BRCA2 | chr13:32913044 | rs398122783 |
BRCA1 | chr17:41246532 | rs80357569 | BRCA1 | chr17:41219669 | rs431825410 | BRCA2 | chr13:32913339 | rs398122786 |
BRCA1 | chr17:41243922 | rs80357571 | BRCA1 | chr17:41245932 | rs587776480 | BRCA2 | chr13:32913456 | rs398122789 |
BRCA1 | chr17:41244633 | rs80357573 | BRCA1 | chr17:41244436 | rs80357920 | BRCA2 | chr13:32913546 | rs398122791 |
BRCA1 | chr17:41245334 | rs80357574 | BRCA1 | chr17:41245960 | rs80357613 | BRCA2 | chr13:32900415 | rs398122793 |
BRCA1 | chr17:41246261 | rs80357576 | BRCA1 | chr17:41256162 | rs80357816 | BRCA2 | chr13:32913707 | rs398122796 |
BRCA1 | chr17:41243812 | rs80357578 | BRCA1 | chr17:41245191 | rs80357820 | BRCA2 | chr13:32907522 | rs431825288 |
BRCA1 | chr17:41203104 | rs80357581 | BRCA1 | chr17:41246302 | rs80357964 | BRCA2 | chr13:32910583 | rs431825292 |
BRCA1 | chr17:41197795 | rs80357582 | BRCA1 | chr17:41246698 | rs80357989 | BRCA2 | chr13:32911332 | rs431825300 |
BRCA1 | chr17:41245279 | rs80357583 | BRCA1 | chr17:41243835 | rs80357552 | BRCA2 | chr13:32911878 | rs431825305 |
BRCA1 | chr17:41246666 | rs80357587 | BRCA1 | chr17:41244955 | rs80357675 | BRCA2 | chr13:32911969 | rs431825307 |
BRCA1 | chr17:41201209 | rs80357590 | BRCA1 | chr17:41234440 | rs80357825 | BRCA2 | chr13:32912271 | rs431825312 |
BRCA1 | chr17:41258506 | rs80357591 | BRCA1 | chr17:41197810 | rs80357973 | BRCA2 | chr13:32912577 | rs431825315 |
BRCA1 | chr17:41246156 | rs80357592 | BRCA1 | chr17:41244454 | rs80357647 | BRCA2 | chr13:32913011 | rs431825321 |
BRCA1 | chr17:41244839 | rs80357594 | BRCA1 | chr17:41276035 | rs80357696 | BRCA2 | chr13:32913870 | rs431825330 |
BRCA1 | chr17:41245105 | rs80357598 | BRCA1 | chr17:41244057 | rs80357877 | BRCA2 | chr13:32914070 | rs431825332 |
BRCA1 | chr17:41246086 | rs80357599 | BRCA1 | chr17:41219663 | rs80357894 | BRCA2 | chr13:32914703 | rs431825338 |
BRCA1 | chr17:41245874 | rs80357600 | BRCA1 | chr17:41244059 | rs80357910 | BRCA2 | chr13:32914889 | rs431825342 |
BRCA1 | chr17:41244543 | rs80357601 | BRCA1 | chr17:41276034 | rs80359877 | BRCA2 | chr13:32915094 | rs431825343 |
BRCA1 | chr17:41256251 | rs80357604 | BRCA1 | chr17:41246456 | rs80359880 | BRCA2 | chr13:32905089 | rs431825350 |
BRCA1 | chr17:41245033 | rs80357607 | BRCA1 | chr17:41197781 | rs273902775 | BRCA2 | chr13:32944670 | rs431825365 |
BRCA1 | chr17:41246427 | rs80357612 | BRCA1 | chr17:41256935 | rs398122659 | BRCA2 | chr13:32953536 | rs431825371 |
BRCA1 | chr17:41244822 | rs80357614 | BRCA1 | chr17:41256905 | rs80359879 | BRCA2 | chr13:32911087 | rs483353111 |
BRCA1 | chr17:41223088 | rs80357615 | BRCA1 | chr17:41228586 | rs273900731 | BRCA2 | chr13:32914590 | rs483353117 |
BRCA1 | chr17:41243728 | rs80357616 | BRCA1 | chr17:41197776 | rs80359873 | BRCA2 | chr13:32929273 | rs483353119 |
BRCA1 | chr17:41246532 | rs80357618 | BRCA1 | chr17:41245347 | rs273898681 | BRCA2 | chr13:32930598 | rs483353120 |
BRCA1 | chr17:41245899 | rs80357619 | BRCA1 | chr17:41228601 | rs80359885 | BRCA2 | chr13:32945095 | rs587776351 |
BRCA1 | chr17:41228526 | rs80357620 | BRCA1 | chr17:41222949 | rs80359876 | BRCA2 | chr13:32913878 | rs587776467 |
BRCA1 | chr17:41244017 | rs80357621 | BRCA1 | chr17:41245894 | rs80359881 | BRCA2 | chr13:32914536 | rs587776468 |
BRCA1 | chr17:41246637 | rs80357622 | BRCA1 | chr17:41243808 | rs80359882 | BRCA2 | chr13:32914767 | rs11571658 |
BRCA1 | chr17:41244293 | rs80357624 | BRCA1 | chr17:41222947 | rs80359884 | BRCA2 | chr13:32906805 | rs80359266 |
BRCA1 | chr17:41245529 | rs80357626 | BRCA1 | chr17:41242939 | rs273900724 | BRCA2 | chr13:32906911 | rs80359276 |
BRCA1 | chr17:41244596 | rs80357627 | BRCA1 | chr17:41219560 | rs8176235 | BRCA2 | chr13:32907004 | rs80359283 |
BRCA1 | chr17:41246773 | rs80357628 | BRCA1 | chr17:41249283 | rs80357090 | BRCA2 | chr13:32907111 | rs80359285 |
BRCA1 | chr17:41197729 | rs80357629 | BRCA1 | chr17:41249306 | rs397509289 | BRCA2 | chr13:32907126 | rs80359286 |
BRCA1 | chr17:41245997 | rs80357630 | BRCA1 | chr17:41249364 | rs587776494 | BRCA2 | chr13:32907214 | rs80359293 |
BRCA1 | chr17:41245072 | rs80357631 | BRCA1 | chr17:41204856 | rs17671533 | BRCA2 | chr13:32907246 | rs80359295 |
BRCA1 | chr17:41243640 | rs80357634 | BRCA1 | chr17:41211653 | rs8176273 | BRCA2 | chr13:32890614 | rs80359298 |
BRCA1 | chr17:41258542 | rs80357637 | BRCA1 | chr17:41213996 | rs8176265 | BRCA2 | chr13:32907469 | rs80359313 |
BRCA1 | chr17:41245531 | rs80357638 | BRCA1 | chr17:41216205 | rs8176257 | BRCA2 | chr13:32911056 | rs80359334 |
BRCA1 | chr17:41251819 | rs80357639 | BRCA1 | chr17:41216933 | rs3785546 | BRCA2 | chr13:32911290 | rs80359348 |
BRCA1 | chr17:41246104 | rs80357648 | BRCA1 | chr17:41218333 | rs4793194 | BRCA2 | chr13:32911302 | rs80359353 |
BRCA1 | chr17:41245307 | rs80357650 | BRCA1 | chr17:41221596 | rs8176225 | BRCA2 | chr13:32911325 | rs80359355 |
BRCA1 | chr17:41245711 | rs80357652 | BRCA1 | chr17:41226033 | rs2236763 | BRCA2 | chr13:32911326 | rs80359356 |
BRCA1 | chr17:41222997 | rs80357653 | BRCA1 | chr17:41226675 | rs2236762 | BRCA2 | chr13:32911328 | rs80359357 |
BRCA1 | chr17:41223040 | rs80357656 | BRCA1 | chr17:41234304 | rs3737559 | BRCA2 | chr13:32911391 | rs80359361 |
BRCA1 | chr17:41245061 | rs80357658 | BRCA1 | chr17:41242285 | rs2070834 | BRCA2 | chr13:32911720 | rs80359378 |
BRCA1 | chr17:41244878 | rs80357659 | BRCA1 | chr17:41242849 | rs2070833 | BRCA2 | chr13:32911754 | rs80359379 |
BRCA1 | chr17:41258514 | rs80357660 | BRCA1 | chr17:41243190 | rs799916 | BRCA2 | chr13:32911992 | rs80359387 |
BRCA1 | chr17:41245992 | rs80357662 | BRCA1 | chr17:41257134 | rs799912 | BRCA2 | chr13:32912037 | rs80359388 |
BRCA1 | chr17:41243968 | rs80357663 | BRCA1 | chr17:41276247 | rs3765640 | BRCA2 | chr13:32912046 | rs80359389 |
BRCA1 | chr17:41245372 | rs80357668 | BRCA2 | chr13:32906729 | rs144848 | BRCA2 | chr13:32912090 | rs80359391 |
BRCA1 | chr17:41245091 | rs80357669 | BRCA2 | chr13:32972574 | rs4987049 | BRCA2 | chr13:32912091 | rs80359392 |
BRCA1 | chr17:41219628 | rs80357672 | BRCA2 | chr13:32921033 | rs28897743 | BRCA2 | chr13:32912172 | rs80359395 |
BRCA1 | chr17:41219659 | rs80357673 | BRCA2 | chr13:32954050 | rs28897756 | BRCA2 | chr13:32890634 | rs80359400 |
BRCA1 | chr17:41209103 | rs80357676 | BRCA2 | chr13:32968940 | rs28897759 | BRCA2 | chr13:32912339 | rs80359405 |
BRCA1 | chr17:41245098 | rs80357679 | BRCA2 | chr13:32911650 | rs41293477 | BRCA2 | chr13:32912351 | rs80359408 |
BRCA1 | chr17:41245275 | rs80357681 | BRCA2 | chr13:32914174 | rs41293497 | BRCA2 | chr13:32912498 | rs80359419 |
BRCA1 | chr17:41258541 | rs80357682 | BRCA2 | chr13:32937506 | rs41293511 | BRCA2 | chr13:32912500 | rs80359420 |
BRCA1 | chr17:41246229 | rs80357683 | BRCA2 | chr13:32937507 | rs41293513 | BRCA2 | chr13:32912529 | rs80359421 |
BRCA1 | chr17:41203128 | rs80357684 | BRCA2 | chr13:32954180 | rs45580035 | BRCA2 | chr13:32912584 | rs80359426 |
BRCA1 | chr17:41244822 | rs80357685 | BRCA2 | chr13:32914274 | rs56253082 | BRCA2 | chr13:32912623 | rs80359429 |
BRCA1 | chr17:41243789 | rs80357687 | BRCA2 | chr13:32911658 | rs79728106 | BRCA2 | chr13:32912901 | rs80359446 |
BRCA1 | chr17:41245477 | rs80357688 | BRCA2 | chr13:32893246 | rs80358391 | BRCA2 | chr13:32900274 | rs80359459 |
BRCA1 | chr17:41246618 | rs80357689 | BRCA2 | chr13:32906718 | rs80358407 | BRCA2 | chr13:32913200 | rs80359464 |
BRCA1 | chr17:41244219 | rs80357692 | BRCA2 | chr13:32906768 | rs80358411 | BRCA2 | chr13:32913301 | rs80359467 |
BRCA1 | chr17:41201203 | rs80357694 | BRCA2 | chr13:32906817 | rs80358413 | BRCA2 | chr13:32913321 | rs80359468 |
BRCA1 | chr17:41246817 | rs80357700 | BRCA2 | chr13:32906876 | rs80358419 | BRCA2 | chr13:32913337 | rs80359469 |
BRCA1 | chr17:41244367 | rs80357702 | BRCA2 | chr13:32907014 | rs80358427 | BRCA2 | chr13:32913368 | rs80359470 |
BRCA1 | chr17:41244786 | rs80357703 | BRCA2 | chr13:32907026 | rs80358428 | BRCA2 | chr13:32913439 | rs80359474 |
BRCA1 | chr17:41243782 | rs80357704 | BRCA2 | chr13:32907029 | rs80358429 | BRCA2 | chr13:32913473 | rs80359476 |
BRCA1 | chr17:41222995 | rs80357705 | BRCA2 | chr13:32907071 | rs80358434 | BRCA2 | chr13:32913534 | rs80359478 |
BRCA1 | chr17:41256174 | rs80357709 | BRCA2 | chr13:32893291 | rs80358435 | BRCA2 | chr13:32913566 | rs80359482 |
BRCA1 | chr17:41243513 | rs80357711 | BRCA2 | chr13:32907143 | rs80358438 | BRCA2 | chr13:32890648 | rs80359483 |
BRCA1 | chr17:41246168 | rs80357714 | BRCA2 | chr13:32907285 | rs80358452 | BRCA2 | chr13:32913656 | rs80359490 |
BRCA1 | chr17:41245393 | rs80357715 | BRCA2 | chr13:32907296 | rs80358455 | BRCA2 | chr13:32913731 | rs80359500 |
BRCA1 | chr17:41215893 | rs80357720 | BRCA2 | chr13:32907304 | rs80358456 | BRCA2 | chr13:32913782 | rs80359503 |
BRCA1 | chr17:41197766 | rs80357721 | BRCA2 | chr13:32907404 | rs80358461 | BRCA2 | chr13:32913795 | rs80359505 |
BRCA1 | chr17:41246162 | rs80357722 | BRCA2 | chr13:32907415 | rs80358464 | BRCA2 | chr13:32913836 | rs80359506 |
BRCA1 | chr17:41245791 | rs80357723 | BRCA2 | chr13:32907434 | rs80358471 | BRCA2 | chr13:32913842 | rs80359507 |
BRCA1 | chr17:41245219 | rs80357725 | BRCA2 | chr13:32907440 | rs80358472 | BRCA2 | chr13:32900657 | rs80359510 |
BRCA1 | chr17:41243921 | rs80357729 | BRCA2 | chr13:32907447 | rs80358474 | BRCA2 | chr13:32900657 | rs80359511 |
BRCA1 | chr17:41209072 | rs80357732 | BRCA2 | chr13:32907470 | rs80358476 | BRCA2 | chr13:32913902 | rs80359512 |
BRCA1 | chr17:41245480 | rs80357733 | BRCA2 | chr13:32910556 | rs80358485 | BRCA2 | chr13:32914087 | rs80359524 |
BRCA1 | chr17:41258546 | rs80357734 | BRCA2 | chr13:32910716 | rs80358494 | BRCA2 | chr13:32914194 | rs80359528 |
BRCA1 | chr17:41246018 | rs80357735 | BRCA2 | chr13:32893373 | rs80358498 | BRCA2 | chr13:32914209 | rs80359529 |
BRCA1 | chr17:41245723 | rs80357736 | BRCA2 | chr13:32910868 | rs80358503 | BRCA2 | chr13:32914210 | rs80359530 |
BRCA1 | chr17:41243463 | rs80357737 | BRCA2 | chr13:32910901 | rs80358504 | BRCA2 | chr13:32914214 | rs80359531 |
BRCA1 | chr17:41245189 | rs80357739 | BRCA2 | chr13:32893396 | rs80358515 | BRCA2 | chr13:32900693 | rs80359533 |
BRCA1 | chr17:41245071 | rs80357740 | BRCA2 | chr13:32911009 | rs80358516 | BRCA2 | chr13:32914270 | rs80359536 |
BRCA1 | chr17:41244614 | rs80357741 | BRCA2 | chr13:32911029 | rs80358518 | BRCA2 | chr13:32914288 | rs80359537 |
BRCA1 | chr17:41215388 | rs80357743 | BRCA2 | chr13:32893420 | rs80358529 | BRCA2 | chr13:32914328 | rs80359542 |
BRCA1 | chr17:41201192 | rs80357744 | BRCA2 | chr13:32911310 | rs80358532 | BRCA2 | chr13:32914445 | rs80359551 |
BRCA1 | chr17:41247865 | rs80357745 | BRCA2 | chr13:32911322 | rs80358533 | BRCA2 | chr13:32914460 | rs80359552 |
BRCA1 | chr17:41244504 | rs80357746 | BRCA2 | chr13:32911373 | rs80358538 | BRCA2 | chr13:32914570 | rs80359557 |
BRCA1 | chr17:41234457 | rs80357748 | BRCA2 | chr13:32911470 | rs80358543 | BRCA2 | chr13:32914690 | rs80359564 |
BRCA1 | chr17:41267776 | rs80357750 | BRCA2 | chr13:32911471 | rs80358544 | BRCA2 | chr13:32914695 | rs80359566 |
BRCA1 | chr17:41203084 | rs80357751 | BRCA2 | chr13:32893444 | rs80358546 | BRCA2 | chr13:32914762 | rs80359571 |
BRCA1 | chr17:41245595 | rs80357753 | BRCA2 | chr13:32890599 | rs80358547 | BRCA2 | chr13:32914827 | rs80359574 |
BRCA1 | chr17:41244956 | rs80357756 | BRCA2 | chr13:32911565 | rs80358550 | BRCA2 | chr13:32903582 | rs80359575 |
BRCA1 | chr17:41251810 | rs80357758 | BRCA2 | chr13:32911568 | rs80358552 | BRCA2 | chr13:32914844 | rs80359576 |
BRCA1 | chr17:41222989 | rs80357761 | BRCA2 | chr13:32911595 | rs80358556 | BRCA2 | chr13:32914866 | rs80359579 |
BRCA1 | chr17:41251845 | rs80357762 | BRCA2 | chr13:32911601 | rs80358557 | BRCA2 | chr13:32914883 | rs80359580 |
BRCA1 | chr17:41234568 | rs80357765 | BRCA2 | chr13:32893460 | rs80358561 | BRCA2 | chr13:32914935 | rs80359589 |
BRCA1 | chr17:41246272 | rs80357766 | BRCA2 | chr13:32911757 | rs80358573 | BRCA2 | chr13:32914937 | rs80359592 |
BRCA1 | chr17:41243754 | rs80357767 | BRCA2 | chr13:32911811 | rs80358578 | BRCA2 | chr13:32914941 | rs80359594 |
BRCA1 | chr17:41246158 | rs80357770 | BRCA2 | chr13:32911854 | rs80358579 | BRCA2 | chr13:32914954 | rs80359596 |
BRCA1 | chr17:41246530 | rs80357774 | BRCA2 | chr13:32911947 | rs80358593 | BRCA2 | chr13:32914960 | rs80359597 |
BRCA1 | chr17:41246419 | rs80357776 | BRCA2 | chr13:32911961 | rs80358595 | BRCA2 | chr13:32915001 | rs80359600 |
BRCA1 | chr17:41243496 | rs80357779 | BRCA2 | chr13:32912240 | rs80358615 | BRCA2 | chr13:32903606 | rs80359604 |
BRCA1 | chr17:41246025 | rs80357782 | BRCA2 | chr13:32912277 | rs80358620 | BRCA2 | chr13:32915083 | rs80359605 |
BRCA1 | chr17:41276048 | rs80357783 | BRCA2 | chr13:32890634 | rs80358622 | BRCA2 | chr13:32915092 | rs80359607 |
BRCA1 | chr17:41245848 | rs80357784 | BRCA2 | chr13:32912304 | rs80358623 | BRCA2 | chr13:32915095 | rs80359608 |
BRCA1 | chr17:41244197 | rs80357785 | BRCA2 | chr13:32912363 | rs80358631 | BRCA2 | chr13:32903610 | rs80359609 |
BRCA1 | chr17:41245249 | rs80357786 | BRCA2 | chr13:32912373 | rs80358632 | BRCA2 | chr13:32915118 | rs80359610 |
BRCA1 | chr17:41242983 | rs80357788 | BRCA2 | chr13:32912414 | rs80358638 | BRCA2 | chr13:32915121 | rs80359611 |
BRCA1 | chr17:41234478 | rs80357790 | BRCA2 | chr13:32912431 | rs80358641 | BRCA2 | chr13:32915168 | rs80359619 |
BRCA1 | chr17:41209105 | rs80357791 | BRCA2 | chr13:32912450 | rs80358644 | BRCA2 | chr13:32915249 | rs80359623 |
BRCA1 | chr17:41245338 | rs80357793 | BRCA2 | chr13:32912459 | rs80358648 | BRCA2 | chr13:32915253 | rs80359624 |
BRCA1 | chr17:41246251 | rs80357794 | BRCA2 | chr13:32890600 | rs80358650 | BRCA2 | chr13:32929015 | rs80359634 |
BRCA1 | chr17:41246481 | rs80357796 | BRCA2 | chr13:32912493 | rs80358652 | BRCA2 | chr13:32929059 | rs80359636 |
BRCA1 | chr17:41243771 | rs80357798 | BRCA2 | chr13:32912587 | rs80358658 | BRCA2 | chr13:32929098 | rs80359638 |
BRCA1 | chr17:41245080 | rs80357799 | BRCA2 | chr13:32912603 | rs80358659 | BRCA2 | chr13:32929201 | rs80359642 |
BRCA1 | chr17:41245331 | rs80357802 | BRCA2 | chr13:32912714 | rs80358663 | BRCA2 | chr13:32929244 | rs80359644 |
BRCA1 | chr17:41276050 | rs80357803 | BRCA2 | chr13:32912777 | rs80358665 | BRCA2 | chr13:32929369 | rs80359647 |
BRCA1 | chr17:41244106 | rs80357808 | BRCA2 | chr13:32912817 | rs80358670 | BRCA2 | chr13:32929404 | rs80359650 |
BRCA1 | chr17:41246283 | rs80357809 | BRCA2 | chr13:32913017 | rs80358683 | BRCA2 | chr13:32929409 | rs80359651 |
BRCA1 | chr17:41244782 | rs80357812 | BRCA2 | chr13:32913080 | rs80358692 | BRCA2 | chr13:32930603 | rs80359653 |
BRCA1 | chr17:41244252 | rs80357815 | BRCA2 | chr13:32913140 | rs80358695 | BRCA2 | chr13:32905130 | rs80359662 |
BRCA1 | chr17:41246037 | rs80357817 | BRCA2 | chr13:32900287 | rs80358702 | BRCA2 | chr13:32930696 | rs80359664 |
BRCA1 | chr17:41246421 | rs80357821 | BRCA2 | chr13:32913351 | rs80358710 | BRCA2 | chr13:32930724 | rs80359666 |
BRCA1 | chr17:41203093 | rs80357823 | BRCA2 | chr13:32913381 | rs80358711 | BRCA2 | chr13:32905141 | rs80359670 |
BRCA1 | chr17:41246863 | rs80357824 | BRCA2 | chr13:32900394 | rs80358717 | BRCA2 | chr13:32931934 | rs80359672 |
BRCA1 | chr17:41244191 | rs80357827 | BRCA2 | chr13:32913425 | rs80358719 | BRCA2 | chr13:32931940 | rs80359673 |
BRCA1 | chr17:41245074 | rs80357830 | BRCA2 | chr13:32913457 | rs80358721 | BRCA2 | chr13:32905149 | rs80359677 |
BRCA1 | chr17:41244990 | rs80357835 | BRCA2 | chr13:32913599 | rs80358735 | BRCA2 | chr13:32905152 | rs80359680 |
BRCA1 | chr17:41246476 | rs80357836 | BRCA2 | chr13:32913651 | rs80358740 | BRCA2 | chr13:32936660 | rs80359683 |
BRCA1 | chr17:41201160 | rs80357838 | BRCA2 | chr13:32913709 | rs80358746 | BRCA2 | chr13:32936673 | rs80359684 |
BRCA1 | chr17:41197777 | rs80357839 | BRCA2 | chr13:32913771 | rs80358751 | BRCA2 | chr13:32937407 | rs80359694 |
BRCA1 | chr17:41244440 | rs80357841 | BRCA2 | chr13:32913778 | rs80358754 | BRCA2 | chr13:32937576 | rs80359700 |
BRCA1 | chr17:41246619 | rs80357844 | BRCA2 | chr13:32913836 | rs80358757 | BRCA2 | chr13:32937585 | rs80359701 |
BRCA1 | chr17:41243784 | rs80357848 | BRCA2 | chr13:32913896 | rs80358763 | BRCA2 | chr13:32937586 | rs80359702 |
BRCA1 | chr17:41245155 | rs80357850 | BRCA2 | chr13:32913920 | rs80358766 | BRCA2 | chr13:32945138 | rs80359714 |
BRCA1 | chr17:41245650 | rs80357851 | BRCA2 | chr13:32913926 | rs80358767 | BRCA2 | chr13:32945142 | rs80359716 |
BRCA1 | chr17:41245587 | rs80357853 | BRCA2 | chr13:32914061 | rs80358778 | BRCA2 | chr13:32945183 | rs80359719 |
BRCA1 | chr17:41243692 | rs80357855 | BRCA2 | chr13:32914106 | rs80358783 | BRCA2 | chr13:32893232 | rs80359722 |
BRCA1 | chr17:41244086 | rs80357857 | BRCA2 | chr13:32914137 | rs80358785 | BRCA2 | chr13:32950847 | rs80359724 |
BRCA1 | chr17:41244291 | rs80357858 | BRCA2 | chr13:32914147 | rs80358789 | BRCA2 | chr13:32950922 | rs80359727 |
BRCA1 | chr17:41246344 | rs80357859 | BRCA2 | chr13:32914148 | rs80358790 | BRCA2 | chr13:32906512 | rs80359735 |
BRCA1 | chr17:41245342 | rs80357860 | BRCA2 | chr13:32914265 | rs80358806 | BRCA2 | chr13:32953948 | rs80359739 |
BRCA1 | chr17:41243033 | rs80357861 | BRCA2 | chr13:32914283 | rs80358807 | BRCA2 | chr13:32953949 | rs80359740 |
BRCA1 | chr17:41245035 | rs80357863 | BRCA2 | chr13:32900700 | rs80358809 | BRCA2 | chr13:32953987 | rs80359743 |
BRCA1 | chr17:41244186 | rs80357865 | BRCA2 | chr13:32900701 | rs80358810 | BRCA2 | chr13:32953999 | rs80359745 |
BRCA1 | chr17:41258490 | rs80357869 | BRCA2 | chr13:32914349 | rs80358814 | BRCA2 | chr13:32954032 | rs80359748 |
BRCA1 | chr17:41215898 | rs80357870 | BRCA2 | chr13:32914356 | rs80358815 | BRCA2 | chr13:32906545 | rs80359755 |
BRCA1 | chr17:41251825 | rs80357872 | BRCA2 | chr13:32914401 | rs80358824 | BRCA2 | chr13:32968879 | rs80359756 |
BRCA1 | chr17:41243849 | rs80357873 | BRCA2 | chr13:32914417 | rs80358825 | BRCA2 | chr13:32968953 | rs80359758 |
BRCA1 | chr17:41215917 | rs80357874 | BRCA2 | chr13:32914451 | rs80358828 | BRCA2 | chr13:32968995 | rs80359762 |
BRCA1 | chr17:41244608 | rs80357876 | BRCA2 | chr13:32914472 | rs80358831 | BRCA2 | chr13:32969004 | rs80359763 |
BRCA1 | chr17:41243718 | rs80357878 | BRCA2 | chr13:32914517 | rs80358838 | BRCA2 | chr13:32969024 | rs80359764 |
BRCA1 | chr17:41246165 | rs80357879 | BRCA2 | chr13:32914529 | rs80358840 | BRCA2 | chr13:32969025 | rs80359765 |
BRCA1 | chr17:41245443 | rs80357880 | BRCA2 | chr13:32914557 | rs80358843 | BRCA2 | chr13:32971113 | rs80359771 |
BRCA1 | chr17:41256954 | rs80357884 | BRCA2 | chr13:32914562 | rs80358844 | BRCA2 | chr13:32906608 | rs80359777 |
BRCA1 | chr17:41245596 | rs80357885 | BRCA2 | chr13:32914616 | rs80358851 | BRCA2 | chr13:32900392 | rs120074205 |
BRCA1 | chr17:41203127 | rs80357886 | BRCA2 | chr13:32914661 | rs80358856 | BRCA2 | chr13:32893408 | rs276174825 |
BRCA1 | chr17:41244638 | rs80357893 | BRCA2 | chr13:32914698 | rs80358859 | BRCA2 | chr13:32911128 | rs276174826 |
BRCA1 | chr17:41219664 | rs80357896 | BRCA2 | chr13:32914731 | rs80358864 | BRCA2 | chr13:32912506 | rs276174839 |
BRCA1 | chr17:41244158 | rs80357900 | BRCA2 | chr13:32914800 | rs80358870 | BRCA2 | chr13:32912630 | rs276174842 |
BRCA1 | chr17:41245776 | rs80357901 | BRCA2 | chr13:32900750 | rs80358871 | BRCA2 | chr13:32912655 | rs276174843 |
BRCA1 | chr17:41243900 | rs80357902 | BRCA2 | chr13:32914874 | rs80358875 | BRCA2 | chr13:32913234 | rs276174847 |
BRCA1 | chr17:41243575 | rs80357904 | BRCA2 | chr13:32914954 | rs80358883 | BRCA2 | chr13:32913557 | rs276174852 |
BRCA1 | chr17:41222990 | rs80357905 | BRCA2 | chr13:32903600 | rs80358884 | BRCA2 | chr13:32914101 | rs276174859 |
BRCA1 | chr17:41209083 | rs80357906 | BRCA2 | chr13:32903611 | rs80358891 | BRCA2 | chr13:32914147 | rs276174861 |
BRCA1 | chr17:41223186 | rs80357907 | BRCA2 | chr13:32915137 | rs80358892 | BRCA2 | chr13:32914817 | rs276174871 |
BRCA1 | chr17:41246038 | rs80357908 | BRCA2 | chr13:32915148 | rs80358893 | BRCA2 | chr13:32929141 | rs276174890 |
BRCA1 | chr17:41245312 | rs80357909 | BRCA2 | chr13:32915260 | rs80358901 | BRCA2 | chr13:32937381 | rs276174901 |
BRCA1 | chr17:41246538 | rs80357911 | BRCA2 | chr13:32905062 | rs80358913 | BRCA2 | chr13:32906610 | rs276174931 |
BRCA1 | chr17:41244932 | rs80357912 | BRCA2 | chr13:32920978 | rs80358920 | BRCA2 | chr13:32911110 | rs397507290 |
BRCA1 | chr17:41245172 | rs80357913 | BRCA2 | chr13:32920985 | rs80358923 | BRCA2 | chr13:32911150 | rs397507291 |
BRCA1 | chr17:41228598 | rs80357916 | BRCA2 | chr13:32929014 | rs80358928 | BRCA2 | chr13:32911501 | rs397507300 |
BRCA1 | chr17:41245552 | rs80357922 | BRCA2 | chr13:32929050 | rs80358936 | BRCA2 | chr13:32912811 | rs397507328 |
BRCA1 | chr17:41209087 | rs80357925 | BRCA2 | chr13:32929105 | rs80358943 | BRCA2 | chr13:32912906 | rs397507332 |
BRCA1 | chr17:41243928 | rs80357926 | BRCA2 | chr13:32929170 | rs80358946 | BRCA2 | chr13:32913204 | rs397507339 |
BRCA1 | chr17:41245736 | rs80357927 | BRCA2 | chr13:32929231 | rs80358951 | BRCA2 | chr13:32915216 | rs397507375 |
BRCA1 | chr17:41244680 | rs80357929 | BRCA2 | chr13:32905107 | rs80358959 | BRCA2 | chr13:32929332 | rs397507386 |
BRCA1 | chr17:41245656 | rs80357932 | BRCA2 | chr13:32930609 | rs80358972 | BRCA2 | chr13:32905114 | rs397507387 |
BRCA1 | chr17:41245636 | rs80357933 | BRCA2 | chr13:32930658 | rs80358979 | BRCA2 | chr13:32937544 | rs397507396 |
BRCA1 | chr17:41199709 | rs80357934 | BRCA2 | chr13:32930687 | rs80358981 | BRCA2 | chr13:32953993 | rs397507418 |
BRCA1 | chr17:41245345 | rs80357936 | BRCA2 | chr13:32931908 | rs80358993 | BRCA2 | chr13:32890619 | rs397507623 |
BRCA1 | chr17:41244535 | rs80357937 | BRCA2 | chr13:32931942 | rs80358994 | BRCA2 | chr13:32912631 | rs397507709 |
BRCA1 | chr17:41219694 | rs80357938 | BRCA2 | chr13:32931982 | rs80358997 | BRCA2 | chr13:32900281 | rs397507739 |
BRCA1 | chr17:41246192 | rs80357939 | BRCA2 | chr13:32905146 | rs80358998 | BRCA2 | chr13:32913432 | rs397507751 |
BRCA1 | chr17:41246872 | rs80357941 | BRCA2 | chr13:32931999 | rs80358999 | BRCA2 | chr13:32929241 | rs397507907 |
BRCA1 | chr17:41244799 | rs80357942 | BRCA2 | chr13:32932018 | rs80359003 | BRCA2 | chr13:32906804 | rs397515635 |
BRCA1 | chr17:41267753 | rs80357943 | BRCA2 | chr13:32932019 | rs80359004 | BRCA2 | chr13:32912470 | rs397515636 |
BRCA1 | chr17:41245349 | rs80357944 | BRCA2 | chr13:32936711 | rs80359011 | BRCA2 | chr13:32913835 | rs398122530 |
BRCA1 | chr17:41199687 | rs80357946 | BRCA2 | chr13:32936722 | rs80359012 | BRCA2 | chr13:32914511 | rs398122545 |
BRCA1 | chr17:41246030 | rs80357947 | BRCA2 | chr13:32936732 | rs80359013 | BRCA2 | chr13:32903583 | rs398122553 |
BRCA1 | chr17:41256263 | rs80357950 | BRCA2 | chr13:32936733 | rs80359014 | BRCA2 | chr13:32915119 | rs398122562 |
BRCA1 | chr17:41267747 | rs80357951 | BRCA2 | chr13:32936740 | rs80359015 | BRCA2 | chr13:32936744 | rs398122593 |
BRCA1 | chr17:41246625 | rs80357953 | BRCA2 | chr13:32936762 | rs80359016 | BRCA2 | chr13:32910745 | rs398122744 |
BRCA1 | chr17:41246460 | rs80357954 | BRCA2 | chr13:32936828 | rs80359025 | BRCA2 | chr13:32912492 | rs398122775 |
BRCA1 | chr17:41245234 | rs80357957 | BRCA2 | chr13:32936830 | rs80359027 | BRCA2 | chr13:32913482 | rs398122790 |
BRCA1 | chr17:41203108 | rs80357959 | BRCA2 | chr13:32937317 | rs80359029 | BRCA2 | chr13:32913428 | rs431825323 |
BRCA1 | chr17:41245285 | rs80357960 | BRCA2 | chr13:32937327 | rs80359031 | BRCA2 | chr13:32913468 | rs431825325 |
BRCA1 | chr17:41246739 | rs80357965 | BRCA2 | chr13:32937335 | rs80359032 | BRCA2 | chr13:32899306 | rs483353080 |
BRCA1 | chr17:41244215 | rs80357966 | BRCA2 | chr13:32937348 | rs80359035 | BRCA2 | chr13:32893278 | rs483353112 |
BRCA1 | chr17:41245073 | rs80357970 | BRCA2 | chr13:32937406 | rs80359046 | BRCA2 | chr13:32913055 | rs483353115 |
BRCA1 | chr17:41219643 | rs80357974 | BRCA2 | chr13:32937423 | rs80359048 | BRCA2 | chr13:32913210 | rs483353116 |
BRCA1 | chr17:41197797 | rs80357976 | BRCA2 | chr13:32937426 | rs80359050 | BRCA2 | chr13:32929225 | rs483353118 |
BRCA1 | chr17:41243582 | rs80357979 | BRCA2 | chr13:32937479 | rs80359058 | BRCA2 | chr13:32931923 | rs483353121 |
BRCA1 | chr17:41243936 | rs80357980 | BRCA2 | chr13:32937504 | rs80359062 | BRCA2 | chr13:32937547 | rs483353122 |
BRCA1 | chr17:41234535 | rs80357981 | BRCA2 | chr13:32937527 | rs80359066 | BRCA2 | chr13:32944690 | rs483353123 |
BRCA1 | chr17:41245346 | rs80357982 | BRCA2 | chr13:32906433 | rs80359068 | BRCA2 | chr13:32912396 | rs80359414 |
BRCA1 | chr17:41246383 | rs80357985 | BRCA2 | chr13:32937558 | rs80359070 | BRCA2 | chr13:32914712 | rs276174867 |
BRCA1 | chr17:41243576 | rs80357987 | BRCA2 | chr13:32944584 | rs80359082 | BRCA2 | chr13:32914759 | rs276174868 |
BRCA1 | chr17:41245193 | rs80357990 | BRCA2 | chr13:32944692 | rs80359099 | BRCA2 | chr13:32944601 | rs276174907 |
BRCA1 | chr17:41244549 | rs80357991 | BRCA2 | chr13:32945094 | rs80359101 | BRCA2 | chr13:32953886 | rs276174916 |
BRCA1 | chr17:41215906 | rs80357997 | BRCA2 | chr13:32945109 | rs80359102 | BRCA2 | chr13:32913721 | rs397507349 |
BRCA1 | chr17:41244749 | rs80357998 | BRCA2 | chr13:32945177 | rs80359112 | BRCA2 | chr13:32944621 | rs397507402 |
BRCA1 | chr17:41199722 | rs80358002 | BRCA2 | chr13:32945180 | rs80359115 | BRCA2 | chr13:32906925 | rs80359277 |
BRCA1 | chr17:41215349 | rs80358004 | BRCA2 | chr13:32945199 | rs80359118 | BRCA2 | chr13:32907378 | rs80359303 |
BRCA1 | chr17:41223256 | rs80358008 | BRCA2 | chr13:32945234 | rs80359121 | BRCA2 | chr13:32907387 | rs80359304 |
BRCA1 | chr17:41199658 | rs80358009 | BRCA2 | chr13:32953469 | rs80359133 | BRCA2 | chr13:32907388 | rs80359305 |
BRCA1 | chr17:41276033 | rs80358010 | BRCA2 | chr13:32953472 | rs80359134 | BRCA2 | chr13:32910595 | rs80359324 |
BRCA1 | chr17:41256280 | rs80358011 | BRCA2 | chr13:32953577 | rs80359140 | BRCA2 | chr13:32910746 | rs80359326 |
BRCA1 | chr17:41243449 | rs80358015 | BRCA2 | chr13:32953632 | rs80359144 | BRCA2 | chr13:32911145 | rs80359340 |
BRCA1 | chr17:41267797 | rs80358018 | BRCA2 | chr13:32953650 | rs80359146 | BRCA2 | chr13:32911297 | rs80359350 |
BRCA1 | chr17:41243051 | rs80358019 | BRCA2 | chr13:32953902 | rs80359148 | BRCA2 | chr13:32911298 | rs80359351 |
BRCA1 | chr17:41246878 | rs80358020 | BRCA2 | chr13:32953903 | rs80359149 | BRCA2 | chr13:32911300 | rs80359352 |
BRCA1 | chr17:41222942 | rs80358023 | BRCA2 | chr13:32953932 | rs80359151 | BRCA2 | chr13:32911304 | rs80359354 |
BRCA1 | chr17:41258471 | rs80358026 | BRCA2 | chr13:32953937 | rs80359152 | BRCA2 | chr13:32911652 | rs80359371 |
BRCA1 | chr17:41234420 | rs80358027 | BRCA2 | chr13:32953939 | rs80359153 | BRCA2 | chr13:32911659 | rs80359372 |
BRCA1 | chr17:41201137 | rs80358028 | BRCA2 | chr13:32953951 | rs80359154 | BRCA2 | chr13:32911681 | rs80359374 |
BRCA1 | chr17:41199721 | rs80358029 | BRCA2 | chr13:32953974 | rs80359156 | BRCA2 | chr13:32911684 | rs80359375 |
BRCA1 | chr17:41251791 | rs80358030 | BRCA2 | chr13:32954009 | rs80359159 | BRCA2 | chr13:32911687 | rs80359376 |
BRCA1 | chr17:41247941 | rs80358033 | BRCA2 | chr13:32954033 | rs80359163 | BRCA2 | chr13:32911765 | rs80359382 |
BRCA1 | chr17:41267738 | rs80358038 | BRCA2 | chr13:32954174 | rs80359170 | BRCA2 | chr13:32912174 | rs80359396 |
BRCA1 | chr17:41203079 | rs80358041 | BRCA2 | chr13:32954208 | rs80359175 | BRCA2 | chr13:32912236 | rs80359403 |
BRCA1 | chr17:41258472 | rs80358042 | BRCA2 | chr13:32954222 | rs80359180 | BRCA2 | chr13:32912352 | rs80359410 |
BRCA1 | chr17:41267742 | rs80358043 | BRCA2 | chr13:32954233 | rs80359183 | BRCA2 | chr13:32912357 | rs80359412 |
BRCA1 | chr17:41226347 | rs80358044 | BRCA2 | chr13:32954282 | rs80359192 | BRCA2 | chr13:32912448 | rs80359417 |
BRCA1 | chr17:41251790 | rs80358047 | BRCA2 | chr13:32968845 | rs80359197 | BRCA2 | chr13:32912540 | rs80359423 |
BRCA1 | chr17:41197820 | rs80358048 | BRCA2 | chr13:32968854 | rs80359198 | BRCA2 | chr13:32912625 | rs80359430 |
BRCA1 | chr17:41256281 | rs80358051 | BRCA2 | chr13:32968855 | rs80359199 | BRCA2 | chr13:32912710 | rs80359435 |
BRCA1 | chr17:41219624 | rs80358053 | BRCA2 | chr13:32968863 | rs80359200 | BRCA2 | chr13:32912946 | rs80359449 |
BRCA1 | chr17:41226540 | rs80358054 | BRCA2 | chr13:32968886 | rs80359205 | BRCA2 | chr13:32912948 | rs80359450 |
BRCA1 | chr17:41256984 | rs80358061 | BRCA2 | chr13:32968925 | rs80359207 | BRCA2 | chr13:32912963 | rs80359451 |
BRCA1 | chr17:41228504 | rs80358063 | BRCA2 | chr13:32968945 | rs80359210 | BRCA2 | chr13:32912964 | rs80359452 |
BRCA1 | chr17:41258552 | rs80358065 | BRCA2 | chr13:32968949 | rs80359211 | BRCA2 | chr13:32912969 | rs80359454 |
BRCA1 | chr17:41215970 | rs80358066 | BRCA2 | chr13:32968951 | rs80359212 | BRCA2 | chr13:32912970 | rs80359455 |
BRCA1 | chr17:41209154 | rs80358069 | BRCA2 | chr13:32969050 | rs80359222 | BRCA2 | chr13:32913043 | rs80359457 |
BRCA1 | chr17:41243050 | rs80358070 | BRCA2 | chr13:32971132 | rs80359230 | BRCA2 | chr13:32913428 | rs80359473 |
BRCA1 | chr17:41201133 | rs80358073 | BRCA2 | chr13:32906576 | rs80359234 | BRCA2 | chr13:32913560 | rs80359479 |
BRCA1 | chr17:41242960 | rs80358076 | BRCA2 | chr13:32972533 | rs80359247 | BRCA2 | chr13:32913621 | rs80359484 |
BRCA1 | chr17:41226345 | rs80358082 | BRCA2 | chr13:32972575 | rs80359251 | BRCA2 | chr13:32913622 | rs80359485 |
BRCA1 | chr17:41258470 | rs80358083 | BRCA2 | chr13:32906644 | rs80359260 | BRCA2 | chr13:32913623 | rs80359486 |
BRCA1 | chr17:41222939 | rs80358086 | BRCA2 | chr13:32906669 | rs80359261 | BRCA2 | chr13:32913633 | rs80359487 |
BRCA1 | chr17:41222941 | rs80358087 | BRCA2 | chr13:32893252 | rs80359262 | BRCA2 | chr13:32913705 | rs80359493 |
BRCA1 | chr17:41219623 | rs80358089 | BRCA2 | chr13:32906743 | rs80359263 | BRCA2 | chr13:32913709 | rs80359494 |
BRCA1 | chr17:41215890 | rs80358094 | BRCA2 | chr13:32906753 | rs80359264 | BRCA2 | chr13:32913714 | rs80359498 |
BRCA1 | chr17:41223257 | rs80358096 | BRCA2 | chr13:32906762 | rs80359265 | BRCA2 | chr13:32913758 | rs80359501 |
BRCA1 | chr17:41203135 | rs80358099 | BRCA2 | chr13:32906834 | rs80359267 | BRCA2 | chr13:32914067 | rs80359520 |
BRCA1 | chr17:41246879 | rs80358108 | BRCA2 | chr13:32906840 | rs80359268 | BRCA2 | chr13:32914068 | rs80359521 |
BRCA1 | chr17:41256279 | rs80358116 | BRCA2 | chr13:32906846 | rs80359269 | BRCA2 | chr13:32914069 | rs80359522 |
BRCA1 | chr17:41256976 | rs80358119 | BRCA2 | chr13:32906848 | rs80359270 | BRCA2 | chr13:32914077 | rs80359523 |
BRCA1 | chr17:41215888 | rs80358124 | BRCA2 | chr13:32906853 | rs80359271 | BRCA2 | chr13:32914113 | rs80359526 |
BRCA1 | chr17:41201212 | rs80358126 | BRCA2 | chr13:32906872 | rs80359272 | BRCA2 | chr13:32914263 | rs80359535 |
BRCA1 | chr17:41276032 | rs80358128 | BRCA2 | chr13:32906880 | rs80359273 | BRCA2 | chr13:32914291 | rs80359538 |
BRCA1 | chr17:41267741 | rs80358131 | BRCA2 | chr13:32906893 | rs80359274 | BRCA2 | chr13:32914340 | rs80359543 |
BRCA1 | chr17:41215391 | rs80358137 | BRCA2 | chr13:32893274 | rs80359275 | BRCA2 | chr13:32914343 | rs80359544 |
BRCA1 | chr17:41199659 | rs80358145 | BRCA2 | chr13:32906922 | rs80359278 | BRCA2 | chr13:32914396 | rs80359547 |
BRCA1 | chr17:41256974 | rs80358146 | BRCA2 | chr13:32906936 | rs80359281 | BRCA2 | chr13:32914438 | rs80359549 |
BRCA1 | chr17:41209068 | rs80358150 | BRCA2 | chr13:32906977 | rs80359282 | BRCA2 | chr13:32914893 | rs80359583 |
BRCA1 | chr17:41197859 | rs80358151 | BRCA2 | chr13:32907023 | rs80359284 | BRCA2 | chr13:32914936 | rs80359591 |
BRCA1 | chr17:41234419 | rs80358152 | BRCA2 | chr13:32893297 | rs80359287 | BRCA2 | chr13:32914978 | rs80359598 |
BRCA1 | chr17:41251899 | rs80358155 | BRCA2 | chr13:32907157 | rs80359288 | BRCA2 | chr13:32915136 | rs80359616 |
BRCA1 | chr17:41258551 | rs80358158 | BRCA2 | chr13:32907162 | rs80359289 | BRCA2 | chr13:32915150 | rs80359617 |
BRCA1 | chr17:41222944 | rs80358162 | BRCA2 | chr13:32907212 | rs80359292 | BRCA2 | chr13:32920970 | rs80359629 |
BRCA1 | chr17:41256985 | rs80358163 | BRCA2 | chr13:32907232 | rs80359294 | BRCA2 | chr13:32929198 | rs80359641 |
BRCA1 | chr17:41215886 | rs80358165 | BRCA2 | chr13:32907263 | rs80359296 | BRCA2 | chr13:32905103 | rs80359645 |
BRCA1 | chr17:41209153 | rs80358173 | BRCA2 | chr13:32907269 | rs80359297 | BRCA2 | chr13:32929369 | rs80359648 |
BRCA1 | chr17:41243451 | rs80358178 | BRCA2 | chr13:32893316 | rs80359299 | BRCA2 | chr13:32905129 | rs80359659 |
BRCA1 | chr17:41203078 | rs80358182 | BRCA2 | chr13:32907320 | rs80359300 | BRCA2 | chr13:32905130 | rs80359663 |
BRCA1 | chr17:41226539 | rs80358189 | BRCA2 | chr13:32907369 | rs80359301 | BRCA2 | chr13:32931916 | rs80359669 |
BRCA1 | chr17:41223028 | rs200432771 | BRCA2 | chr13:32907422 | rs80359306 | BRCA2 | chr13:32937573 | rs80359699 |
BRCA1 | chr17:41246382 | rs273897653 | BRCA2 | chr13:32907421 | rs80359307 | BRCA2 | chr13:32944547 | rs80359707 |
BRCA1 | chr17:41246161 | rs273897658 | BRCA2 | chr13:32907428 | rs80359308 | BRCA2 | chr13:32945140 | rs80359715 |
BRCA1 | chr17:41258535 | rs273897662 | BRCA2 | chr13:32907428 | rs80359309 | BRCA2 | chr13:32950887 | rs80359726 |
BRCA1 | chr17:41245853 | rs273897664 | BRCA2 | chr13:32907430 | rs80359310 | BRCA2 | chr13:32953894 | rs80359734 |
BRCA1 | chr17:41258496 | rs273897665 | BRCA2 | chr13:32907446 | rs80359311 | BRCA2 | chr13:32953913 | rs80359737 |
BRCA1 | chr17:41258481 | rs273898673 | BRCA2 | chr13:32907457 | rs80359312 | BRCA2 | chr13:32968844 | rs80359754 |
BRCA1 | chr17:41245489 | rs273898674 | BRCA2 | chr13:32907503 | rs80359314 | BRCA2 | chr13:32971046 | rs80359769 |
BRCA1 | chr17:41245406 | rs273898679 | BRCA2 | chr13:32907504 | rs80359315 | BRCA2 | chr13:32972349 | rs80359775 |
BRCA1 | chr17:41244862 | rs273899687 | BRCA2 | chr13:32910421 | rs80359316 | BRCA2 | chr13:32913608 | rs276174853 |
BRCA1 | chr17:41256280 | rs273899695 | BRCA2 | chr13:32910518 | rs80359317 | BRCA2 | chr13:32913637 | rs276174854 |
BRCA1 | chr17:41244522 | rs273899696 | BRCA2 | chr13:32910528 | rs80359318 | BRCA2 | chr13:32914133 | rs276174860 |
BRCA1 | chr17:41244451 | rs273899698 | BRCA2 | chr13:32893350 | rs80359320 | BRCA2 | chr13:32914210 | rs276174862 |
BRCA1 | chr17:41244444 | rs273899699 | BRCA2 | chr13:32910584 | rs80359322 | BRCA2 | chr13:32914701 | rs276174866 |
BRCA1 | chr17:41244322 | rs273899703 | BRCA2 | chr13:32910586 | rs80359323 | BRCA2 | chr13:32954278 | rs276174918 |
BRCA1 | chr17:41244205 | rs273899705 | BRCA2 | chr13:32910704 | rs80359325 | BRCA2 | chr13:32912619 | rs397507323 |
BRCA1 | chr17:41244131 | rs273899706 | BRCA2 | chr13:32910779 | rs80359327 | BRCA2 | chr13:32912907 | rs397507333 |
BRCA1 | chr17:41243967 | rs273900710 | BRCA2 | chr13:32910822 | rs80359328 | BRCA2 | chr13:32913413 | rs397507344 |
BRCA1 | chr17:41243686 | rs273900718 | BRCA2 | chr13:32910927 | rs80359329 | BRCA2 | chr13:32914095 | rs397507356 |
BRCA1 | chr17:41234564 | rs273900728 | BRCA2 | chr13:32910938 | rs80359330 | BRCA2 | chr13:32945153 | rs397507406 |
BRCA1 | chr17:41226507 | rs273900736 | BRCA2 | chr13:32910942 | rs80359331 | BRCA2 | chr13:32915126 | rs397507871 |
BRCA1 | chr17:41215392 | rs273901746 | BRCA2 | chr13:32911018 | rs80359332 | BRCA2 | chr13:32914076 | rs398122535 |
BRCA1 | chr17:41215348 | rs273901751 | BRCA2 | chr13:32911037 | rs80359333 | BRCA2 | chr13:32914551 | rs398122546 |
BRCA1 | chr17:41209068 | rs273901754 | BRCA2 | chr13:32911075 | rs80359335 | BRCA2 | chr13:32914897 | rs398122556 |
BRCA1 | chr17:41267798 | rs273902791 | BRCA2 | chr13:32911080 | rs80359338 | BRCA2 | chr13:32920972 | rs398122571 |
BRCA1 | chr17:41246700 | rs273902792 | BRCA2 | chr13:32893409 | rs80359339 | BRCA2 | chr13:32907014 | rs398122726 |
BRCA1 | chr17:41246644 | rs273903793 | BRCA2 | chr13:32893412 | rs80359341 | BRCA2 | chr13:32912348 | rs431825313 |
BRCA1 | chr17:41246584 | rs273903794 | BRCA2 | chr13:32911176 | rs80359342 | BRCA2 | chr13:32907210 | rs80359291 |
BRCA1 | chr17:41243923 | rs387906564 | BRCA2 | chr13:32890623 | rs80359343 | BRCA2 | chr13:32907370 | rs80359302 |
BRCA1 | chr17:41245820 | rs397507192 | BRCA2 | chr13:32911223 | rs80359344 | BRCA2 | chr13:32910576 | rs80359321 |
BRCA1 | chr17:41245694 | rs397507193 | BRCA2 | chr13:32893422 | rs80359345 | BRCA2 | chr13:32911559 | rs80359369 |
BRCA1 | chr17:41245627 | rs397507194 | BRCA2 | chr13:32911252 | rs80359346 | BRCA2 | chr13:32911662 | rs80359373 |
BRCA1 | chr17:41245576 | rs397507195 | BRCA2 | chr13:32911278 | rs80359347 | BRCA2 | chr13:32912629 | rs80359431 |
BRCA1 | chr17:41245124 | rs397507200 | BRCA2 | chr13:32911290 | rs80359349 | BRCA2 | chr13:32912890 | rs80359444 |
BRCA1 | chr17:41244440 | rs397507209 | BRCA2 | chr13:32911328 | rs80359358 | BRCA2 | chr13:32900282 | rs80359463 |
BRCA1 | chr17:41244374 | rs397507210 | BRCA2 | chr13:32911334 | rs80359359 | BRCA2 | chr13:32913649 | rs80359488 |
BRCA1 | chr17:41256251 | rs397507214 | BRCA2 | chr13:32911449 | rs80359365 | BRCA2 | chr13:32913709 | rs80359495 |
BRCA1 | chr17:41244196 | rs397507215 | BRCA2 | chr13:32911543 | rs80359367 | BRCA2 | chr13:32913974 | rs80359516 |
BRCA1 | chr17:41244045 | rs397507216 | BRCA2 | chr13:32911560 | rs80359368 | BRCA2 | chr13:32914108 | rs80359525 |
BRCA1 | chr17:41243865 | rs397507217 | BRCA2 | chr13:32911638 | rs80359370 | BRCA2 | chr13:32914560 | rs80359555 |
BRCA1 | chr17:41243723 | rs397507220 | BRCA2 | chr13:32911691 | rs80359377 | BRCA2 | chr13:32914574 | rs80359558 |
BRCA1 | chr17:41243696 | rs397507222 | BRCA2 | chr13:32911756 | rs80359380 | BRCA2 | chr13:32914894 | rs80359584 |
BRCA1 | chr17:41243557 | rs397507224 | BRCA2 | chr13:32911761 | rs80359381 | BRCA2 | chr13:32914897 | rs80359585 |
BRCA1 | chr17:41228602 | rs397507229 | BRCA2 | chr13:32911786 | rs80359383 | BRCA2 | chr13:32914899 | rs80359586 |
BRCA1 | chr17:41228596 | rs397507230 | BRCA2 | chr13:32911846 | rs80359384 | BRCA2 | chr13:32914938 | rs80359593 |
BRCA1 | chr17:41228562 | rs397507231 | BRCA2 | chr13:32911946 | rs80359385 | BRCA2 | chr13:32915150 | rs80359618 |
BRCA1 | chr17:41251873 | rs397507236 | BRCA2 | chr13:32911950 | rs80359386 | BRCA2 | chr13:32915321 | rs80359626 |
BRCA1 | chr17:41219631 | rs397507239 | BRCA2 | chr13:32912062 | rs80359390 | BRCA2 | chr13:32915325 | rs80359627 |
BRCA1 | chr17:41201158 | rs397507249 | BRCA2 | chr13:32890633 | rs80359393 | BRCA2 | chr13:32921016 | rs80359631 |
BRCA1 | chr17:41197709 | rs397507254 | BRCA2 | chr13:32912130 | rs80359394 | BRCA2 | chr13:32921029 | rs80359632 |
BRCA1 | chr17:41245596 | rs397508922 | BRCA2 | chr13:32912177 | rs80359397 | BRCA2 | chr13:32905141 | rs80359671 |
BRCA1 | chr17:41245351 | rs397508949 | BRCA2 | chr13:32912181 | rs80359398 | BRCA2 | chr13:32905145 | rs80359675 |
BRCA1 | chr17:41245307 | rs397508953 | BRCA2 | chr13:32890633 | rs80359399 | BRCA2 | chr13:32936764 | rs80359686 |
BRCA1 | chr17:41244954 | rs397508984 | BRCA2 | chr13:32912209 | rs80359401 | BRCA2 | chr13:32936767 | rs80359687 |
BRCA1 | chr17:41244865 | rs397508997 | BRCA2 | chr13:32912229 | rs80359402 | BRCA2 | chr13:32953959 | rs80359741 |
BRCA1 | chr17:41244743 | rs397509012 | BRCA2 | chr13:32912329 | rs80359404 | BRCA2 | chr13:32907409 | rs276174813 |
BRCA1 | chr17:41244593 | rs397509027 | BRCA2 | chr13:32912346 | rs80359406 | BRCA2 | chr13:32907411 | rs276174814 |
BRCA1 | chr17:41244269 | rs397509050 | BRCA2 | chr13:32912352 | rs80359409 | BRCA2 | chr13:32912550 | rs397507322 |
BRCA1 | chr17:41243496 | rs397509132 | BRCA2 | chr13:32912352 | rs80359411 | BRCA2 | chr13:32912897 | rs397507331 |
BRCA1 | chr17:41243476 | rs397509136 | BRCA2 | chr13:32912403 | rs80359415 | BRCA2 | chr13:32914825 | rs397507369 |
BRCA1 | chr17:41234577 | rs397509151 | BRCA2 | chr13:32912411 | rs80359416 | BRCA2 | chr13:32906441 | rs397507400 |
BRCA1 | chr17:41222940 | rs397509211 | BRCA2 | chr13:32890600 | rs80359418 | BRCA2 | chr13:32911718 | rs397507659 |
BRCA1 | chr17:41215931 | rs397509228 | BRCA2 | chr13:32912540 | rs80359422 | BRCA2 | chr13:32914884 | rs398122555 |
BRCA1 | chr17:41215889 | rs397509231 | BRCA2 | chr13:32912568 | rs80359424 | BRCA2 | chr13:32918712 | rs398122568 |
BRCA1 | chr17:41201213 | rs397509264 | BRCA2 | chr13:32899303 | rs80359425 | BRCA2 | chr13:32911184 | rs398122752 |
BRCA1 | chr17:41201203 | rs397509268 | BRCA2 | chr13:32899306 | rs80359427 | BRCA2 | chr13:32910963 | rs276174823 |
BRCA1 | chr17:41199682 | rs397509284 | BRCA2 | chr13:32912622 | rs80359428 | BRCA2 | chr13:32913223 | rs276174846 |
BRCA1 | chr17:41197746 | rs397509295 | BRCA2 | chr13:32912661 | rs80359433 | BRCA2 | chr13:32936775 | rs276174897 |
BRCA1 | chr17:41267798 | rs397509326 | BRCA2 | chr13:32912680 | rs80359434 | BRCA2 | chr13:32929175 | rs397507383 |
BRCA1 | chr17:41246455 | rs398122627 | BRCA2 | chr13:32912750 | rs80359436 | BRCA2 | chr13:32911076 | rs80359336 |
BRCA1 | chr17:41246256 | rs398122629 | BRCA2 | chr13:32912763 | rs80359437 | BRCA2 | chr13:32911078 | rs80359337 |
BRCA1 | chr17:41246221 | rs398122630 | BRCA2 | chr13:32912768 | rs80359438 | BRCA2 | chr13:32913709 | rs80359496 |
BRCA1 | chr17:41246212 | rs398122631 | BRCA2 | chr13:32912775 | rs80359439 | BRCA2 | chr13:32914772 | rs80359572 |
BRCA1 | chr17:41246187 | rs398122632 | BRCA2 | chr13:32912776 | rs80359440 | BRCA2 | chr13:32914503 | rs397507362 |
BRCA1 | chr17:41258544 | rs398122635 | BRCA2 | chr13:32912806 | rs80359441 | BRCA2 | chr13:32913709 | rs80359497 |
BRCA1 | chr17:41246036 | rs398122636 | BRCA2 | chr13:32912831 | rs80359443 | BRCA2 | chr13:32914774 | rs80359573 |
BRCA1 | chr17:41245920 | rs398122640 | BRCA2 | chr13:32912915 | rs80359447 | BRCA2 | chr13:32954002 | rs80359746 |
BRCA1 | chr17:41245804 | rs398122641 | BRCA2 | chr13:32912941 | rs80359448 | BRCA2 | chr13:32914926 | rs397507371 |
BRCA1 | chr17:41245789 | rs398122642 | BRCA2 | chr13:32912970 | rs80359453 | BRCA2 | chr13:32906506 | rs276174914 |
BRCA1 | chr17:41245673 | rs398122646 | BRCA2 | chr13:32913038 | rs80359456 | BRCA2 | chr13:32929402 | rs80359649 |
BRCA1 | chr17:41245627 | rs398122650 | BRCA2 | chr13:32913046 | rs80359458 | BRCA2 | chr13:32937539 | rs398122599 |
BRCA1 | chr17:41245162 | rs398122657 | BRCA2 | chr13:32913123 | rs80359460 | BRCA2 | chr13:32911422 | rs80359364 |
BRCA1 | chr17:41256936 | rs398122661 | BRCA2 | chr13:32913123 | rs80359461 | BRCA2 | chr13:32953647 | rs276174915 |
BRCA1 | chr17:41244894 | rs398122663 | BRCA2 | chr13:32913130 | rs80359462 | BRCA2 | chr13:32915235 | rs80359622 |
BRCA1 | chr17:41244862 | rs398122664 | BRCA2 | chr13:32913289 | rs80359465 | BRCA2 | chr13:32914312 | rs80359539 |
BRCA1 | chr17:41244800 | rs398122667 | BRCA2 | chr13:32913300 | rs80359466 | BRCA2 | chr13:32930725 | rs80359667 |
BRCA1 | chr17:41244774 | rs398122669 | BRCA2 | chr13:32913396 | rs80359471 | BRCA2 | chr13:32971074 | rs397508062 |
BRCA1 | chr17:41244344 | rs398122673 | BRCA2 | chr13:32913427 | rs80359472 | BRCA2 | chr13:32913762 | rs80359502 |
BRCA1 | chr17:41243876 | rs398122677 | BRCA2 | chr13:32913457 | rs80359475 | BRCA2 | chr13:32912864 | rs80358672 |
BRCA1 | chr17:41243454 | rs398122681 | BRCA2 | chr13:32913527 | rs80359477 | BRCA2 | chr13:32972884 | rs1801426 |
BRCA1 | chr17:41234424 | rs398122685 | BRCA2 | chr13:32913565 | rs80359480 | BRCA2 | chr13:32888021 | rs9534160 |
BRCA1 | chr17:41226530 | rs398122687 | BRCA2 | chr13:32913565 | rs80359481 | BRCA2 | chr13:32888473 | rs206115 |
BRCA1 | chr17:41215971 | rs398122690 | BRCA2 | chr13:32913650 | rs80359489 | BRCA2 | chr13:32889363 | rs3092989 |
BRCA1 | chr17:41215357 | rs398122692 | BRCA2 | chr13:32913672 | rs80359491 | BRCA2 | chr13:32889792 | rs206118 |
BRCA1 | chr17:41197821 | rs398122699 | BRCA2 | chr13:32900637 | rs80359492 | BRCA2 | chr13:32890026 | rs9562605 |
BRCA1 | chr17:41247862 | rs398122706 | BRCA2 | chr13:32913730 | rs80359499 | BRCA2 | chr13:32891706 | rs206120 |
BRCA1 | chr17:41246612 | rs398122709 | BRCA2 | chr13:32913843 | rs80359508 | BRCA2 | chr13:32893791 | rs9534174 |
BRCA1 | chr17:41267747 | rs431825385 | BRCA2 | chr13:32913843 | rs80359509 | BRCA2 | chr13:32900149 | rs3783265 |
BRCA1 | chr17:41246114 | rs431825386 | BRCA2 | chr13:32913946 | rs80359513 | BRCA2 | chr13:32900933 | rs3752451 |
BRCA1 | chr17:41256212 | rs431825397 | BRCA2 | chr13:32913958 | rs80359514 | BRCA2 | chr13:32908629 | rs1029304 |
BRCA1 | chr17:41243789 | rs431825398 | BRCA2 | chr13:32913963 | rs80359515 | BRCA2 | chr13:32920618 | rs206079 |
BRCA1 | chr17:41242959 | rs431825406 | BRCA2 | chr13:32913984 | rs80359517 | BRCA2 | chr13:32921536 | rs11571684 |
BRCA1 | chr17:41199657 | rs431825417 | BRCA2 | chr13:32914018 | rs80359518 | BRCA2 | chr13:32921944 | rs9567578 |
BRCA1 | chr17:41215945 | rs483353099 | BRCA2 | chr13:32914034 | rs80359519 | BRCA2 | chr13:32922136 | rs206081 |
BRCA1 | chr17:41251875 | rs483353104 | BRCA2 | chr13:32914173 | rs80359527 | BRCA2 | chr13:32926944 | rs721185 |
BRCA1 | chr17:41215890 | rs587776491 | BRCA2 | chr13:32914216 | rs80359532 | BRCA2 | chr13:32927894 | rs9943876 |
BRCA1 | chr17:41244518 | rs80357510 | BRCA2 | chr13:32914255 | rs80359534 | BRCA2 | chr13:32928202 | rs9943888 |
BRCA1 | chr17:41245210 | rs80357515 | BRCA2 | chr13:32914315 | rs80359540 | BRCA2 | chr13:32942956 | rs3837580 |
BRCA1 | chr17:41245670 | rs80357516 | BRCA2 | chr13:32914320 | rs80359541 | BRCA2 | chr13:32944056 | rs9634672 |
BRCA1 | chr17:41243788 | rs80357520 | BRCA2 | chr13:32914349 | rs80359545 | BRCA2 | chr13:32951111 | rs3764791 |
BRCA1 | chr17:41244218 | rs80357525 | BRCA2 | chr13:32914355 | rs80359546 | BRCA2 | chr13:32951115 | rs3764792 |
BRCA1 | chr17:41243035 | rs80357529 | BRCA2 | chr13:32914423 | rs80359548 | BRCA2 | chr13:32956757 | rs206146 |
BRCA1 | chr17:41226489 | rs80357534 | BRCA2 | chr13:32914438 | rs80359550 | BRCA2 | chr13:32959199 | rs2238162 |
BRCA1 | chr17:41276043 | rs80357536 | BRCA2 | chr13:32914493 | rs80359553 | BRCA2 | chr13:32959240 | rs11571789 |
BRCA1 | chr17:41244804 | rs80357540 | BRCA2 | chr13:32914516 | rs80359554 | BRCA2 | chr13:32959534 | rs542551 |
BRCA1 | chr17:41244889 | rs80357541 | BRCA2 | chr13:32914563 | rs80359556 | BRCA2 | chr13:32959839 | rs2238163 |
BRCA1 | chr17:41226397 | rs80357542 | BRCA2 | chr13:32914595 | rs80359559 | BRCA2 | chr13:32963947 | rs11571805 |
BRCA1 | chr17:41246221 | rs80357543 | BRCA2 | chr13:32900729 | rs80359560 | BRCA2 | chr13:32965310 | rs206340 |
BRCA1 | chr17:41245157 | rs80357546 | BRCA2 | chr13:32914621 | rs80359561 | BRCA2 | chr13:32970031 | rs1012130 |
BRCA1 | chr17:41244494 | rs80357547 | BRCA2 | chr13:32914646 | rs80359562 | BRCA2 | chr13:32970586 | rs517118 |
BRCA1 | chr17:41258518 | rs80357550 | BRCA2 | chr13:32914670 | rs80359563 | BRCA2 | chr13:32970736 | rs1012129 |
BRCA1 | chr17:41245291 | rs80357557 | BRCA2 | chr13:32914693 | rs80359565 | BRCA2 | chr13:32973012 | rs15869 |
本发明具有以下优点:(1)特异性强:针对特定SNP设计的引物,获得BRCA基因特定位置附近的全部碱基序列,特异性极强;(2)灵敏度高,检测灵敏度达到0.01%;(3)检测通量高,一次反应可以检测两千多个位点;(4)结果判读明确客观,检测结果直接反映碱基序列,判读结果更直观明确;(5)安全,整个体系不包含有毒有害物质,对试验人员以及环境都无危害。
本发明全面综合了对乳腺癌及卵巢癌具有检测意义的相关易感SNP位点,对各引物的序列以及实验反应体系进行优化,显示出检测能力的强大优势,不仅使得检测简单易行,而且具有较高的准确度、特异性以及可重复性,对乳腺癌及卵巢癌相关易感SNP位点具有检测通量高、特异性强、不易污染、安全性高的优点,检测结果具有较好的准确性和重复性,对乳腺癌和卵巢癌易感人群,尤其是对具有这两种癌症家族遗传史的人群有一定的辅助诊断和提示作用。
附图说明
图1是样本文库构建完整性分析图。
图2是样本上机测试数据分析图。
具体实施方式
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解,在阅读了本发明的内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本发明所限定的范围。
实施例1:乳腺癌病人BRCA基因突变筛选
一、实验材料
1.本实验中涉及的20例临床血液样本来自浙江大学医学院附属第一医院。样本采集后,立即放入-80度冰箱中保存。
2.所有引物纯度应达到电泳级(PAGE)或HPLC级,不含杂带。提供合成机构出具的合成产物的质检证明,如PAGE电泳结果或HPLC分析图谱,证明使用PAGE或者HPLC纯化后应有明显单峰PAGE或者HPLC纯化图谱,浓度为10ng/μl备用。
3.所有试剂购买自正规厂家:多重PCR酶(KAPA公司)、Ampure磁珠(BeckmanCoulter公司)、PGMTemplateOT2kit、PGMSequencingOT2kit(LifeTechnologies公司)。
二、主要仪器
IonTorrentPGM测序仪、Qubit2.0荧光定量仪、高速离心机、水浴锅、漩涡震荡仪、冰箱、烘箱、灭菌锅。
三、实验设计
检测15例正常人血液样本和5例有乳腺癌家族史患者易感SNP位点,根据检测结果确定SNP位点的类型。
四、反应体系及程序
1.根据实验室现有实验基础和经验研究,及参考IonTorrentPGM上机测试的操作规程和多重PCR扩增要求,制定的多重反应体系如下:MasterMix11μl、包含SEQNO:1~SEQNO:448引物的引物panel5.5μl、待测基因4.5μl。
MasterMix组成为:PCRbuffer(5×)4μl、MgCl21.5μl、Taq酶1.5μl、ddH2O4μl。
2.根据以上反应体系进行多重PCR扩增反应程序:95℃预变性3分钟,聚合酶链式反应扩增阶段:95℃变性15s,60℃退火30s,72℃延伸20s,并进行13个循环。实验完成后,对实验结果进行数据处理与分析。
3.多重反应完成后进行文库构建和上机测试,模板文库构建过程包括末端补平修复、末端连接测序接头、模板扩增和纯化,所述反应体系中包含0.2-1U末端补平酶、0.2-1U连接酶、0.2-1U扩增Taq酶、10-50mM测序接头A和P1、1-10×Buffer和0.2-1.8×Ampure纯化磁珠等试剂。
文库构建过程中使用的Ampure磁珠用量为:末端补平后进行纯化的磁珠为70μl体系中加入120μl的Ampure磁珠;连接接头后的纯化步骤,70μl反应体系中加入70μl的Ampure磁珠;两步法片段选择过程中,第一步200bp左右的片段及100μl反应体系中加入90μl的Ampure磁珠,第二步产物中加入20μl的Ampure磁珠;扩增后纯化步骤中,50μl的体系加入70μl的Ampure磁珠。纯化后的产物按照操作规程进行上机测试。
文库构建具体步骤如下:
1.末端补平修复:末端补平酶混合物20μl和DNA模板50μl混合后20℃孵育30min;
2.末端补平后纯化步骤:加入120μlAmpure纯化磁珠吸附DNA片段,80%乙醇洗两次后晾干加水溶解;
3.测序接头连接步骤:测序接头A和P1各10μl与20μl补平后的产物混合,20℃孵育15min,随后65℃孵育5min;
4.连接完成后采用不同浓度的Ampure磁珠进行纯化和片段选择;
5.模板扩增:在体系中加入纯化后的产物20μl,扩增Taq酶混合物25μl,通用引物5μl进行PCR扩增。反应程序为95-98℃30-45s预变性;95-98℃10-15s,60-65℃20-40s,68-72℃20-45s循环8-12次扩增;68-72℃50-60s,4℃保存;
6.扩增后纯化:扩增产物中加入70μlAmpure磁珠进行吸附,80%乙醇洗两次后晾干加水溶解。
图1是文库构建完成后的片段分布图,横坐标代表片段的长度,纵坐标代表片段的浓度(含量)。按照实验方案的设定,经引物panel多重扩增和文库构建后,目的产物应该是130-260bp左右,图1说明实际产物与实验设计相符合。
图2是样本上机测试数据分析图,是经过序列剪切、拼接以及位点分析等数据分析处理,而获得的初步的突变位点概况图,经数据分析可得出易感基因上的热点SNP数。
五、实验结果与分析
实验结束以后,对获得的测序数据进行分析,根据软件分析的结果,筛选出与参考基因组hg19不同的位点。通过比对设计的引物panel和位点信息,筛选出BRCA基因上SNP位点。参考基因组hg19是人类(Homosapiens)标准参考基因组(GRCh37/hg19),是国际通用作为筛选目标序列突变位点或SNP位点的参考基因序列,NCBIGenBankassemblyaccession:GCA_000001405.1。
根据收集的样本检测情况,去除正常的SNP位点,5例乳腺癌家族史患者在BRCA基因上共检测出26个易感SNP位点,结果如表3所示。
表3中位点名称包含以下信息:基因编号+(基因名称)+突变碱基序列+(氨基酸变化),基因名称是指被检测位点所在的基因,RS编号为NCBI网站SNP数据库统一编号、染色体是指被检测位点所在的染色体位置、起始位置是指被检测位点所在染色体上的起始位置。
表35例乳腺癌家族史患者检测结果
SNP位点名称 | 基因名称 | RS编号 | 染色体 | 起始位置 |
NM_000059.3(BRCA2):c.9371A>T(p.Asn3124Ile) | BRCA2 | 28897759 | 13 | 32968940 |
NM_000059.3(BRCA2):c.2376C>A(p.Tyr792Ter) | BRCA2 | 80358503 | 13 | 32910868 |
NM_000059.3(BRCA2):c.37G>T(p.Glu13Ter) | BRCA2 | 80358622 | 13 | 32890634 |
NM_000059.3(BRCA2):c.3812C>A(p.Ser1271Ter) | BRCA2 | 80358623 | 13 | 32912304 |
NM_000059.3(BRCA2):c.4965C>G(p.Tyr1655Ter) | BRCA2 | 80358721 | 13 | 32913457 |
NM_000059.3(BRCA2):c.4965C>A(p.Tyr1655Ter) | BRCA2 | 80358721 | 13 | 32913457 |
NM_000059.3(BRCA2):c.581G>A(p.Trp194Ter) | BRCA2 | 80358809 | 13 | 32900700 |
NM_000059.3(BRCA2):c.582G>A(p.Trp194Ter) | BRCA2 | 80358810 | 13 | 32900701 |
NM_000059.3(BRCA2):c.688A>T(p.Lys230Ter) | BRCA2 | 80358913 | 13 | 32905062 |
NM_007294.3(BRCA1):c.3253dupA(p.Arg1085Lysfs) | BRCA1 | 80357517 | 17 | 41244295 |
NM_007294.3(BRCA1):c.2835dupT(p.Ile946Tyrfs) | BRCA1 | 80357519 | 17 | 41244713 |
NM_007294.3(BRCA1):c.2074delC(p.His692Metfs) | BRCA1 | 80357554 | 17 | 41245474 |
NM_007294.3(BRCA1):c.882delA(p.Asp295Thrfs) | BRCA1 | 80357587 | 17 | 41246666 |
NM_007294.3(BRCA1):c.4843dupG(p.Ala1615Glyfs) | BRCA1 | 80357615 | 17 | 41223088 |
NM_007294.3(BRCA1):c.3820dupG(p.Val1274Glyfs) | BRCA1 | 80357616 | 17 | 41243728 |
NM_007294.3(BRCA1):c.5274delA(p.Lys1759Argfs) | BRCA1 | 80357732 | 17 | 41209072 |
NM_007294.3(BRCA1):c.668delA(p.Lys223Argfs) | BRCA1 | 80357745 | 17 | 41247865 |
NM_007294.3(BRCA1):c.2468delG(p.Arg823Lysfs) | BRCA1 | 80357799 | 17 | 41245080 |
NM_007294.3(BRCA1):c.195delG(p.Asn66Metfs) | BRCA1 | 80357869 | 17 | 41258490 |
NM_007294.3(BRCA1):c.4391delC(p.Pro1464Leufs) | BRCA1 | 80357916 | 17 | 41228598 |
NM_007294.3(BRCA1):c.2475delC(p.Asp825Glufs) | BRCA1 | 80357970 | 17 | 41245073 |
NM_007294.3(BRCA1):c.80+1G>T | BRCA1 | 80358010 | 17 | 41276033 |
NM_007294.3(BRCA1):c.134+5G>A | BRCA1 | 80358038 | 17 | 41267738 |
NM_007294.3(BRCA1):c.212+3A>G | BRCA1 | 80358083 | 17 | 41258470 |
NM_007294.3(BRCA1):c.4986+6T>C | BRCA1 | 80358086 | 17 | 41222939 |
由表3可见,本发明检测的结果与临床检测结果一致,乳腺癌家族史患者在表中的热点SPN位点上有突变,而正常人群则没有。这也表明乳腺癌家族史患者患有乳腺癌的风险较正常人高,本发明可以较好地作为乳腺癌早期发现和治疗的辅助手段。
本发明的引物偏向性扩增的程度低,各引物之间相互干扰性小,特异性强,扩增效果好,对乳腺癌及卵巢癌相关易感SNP位点具有检测通量高、特异性强、不易污染、安全性高的优点,检测结果具有较好的准确性和重复性,对结乳腺癌和卵巢癌易感人群,尤其是对具有这两种癌症家族遗传史的人群有一定的辅助诊断和提示作用。
以上所述的仅是本发明的优选实施方式,应当指出,对于本领域的普通技术人员来说,在不脱离本发明创造构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。
Claims (3)
1.BRCA基因易感SNP位点检测组合物,其特征在于,所述BRCA基因易感SNP位点检测组合物包括SEQNO:1~SEQNO:448的引物;
所述SEQNO:1~SEQNO:448引物的序列如下:
2.根据权利要求1所述的BRCA基因易感SNP位点检测组合物,其特征在于,所述BRCA基因易感SNP位点检测组合物包括:MasterMix11μl、包含所述SEQNO:1~SEQNO:448引物的引物panel5.5μl、待测DNA样品4.5μl;
所述MasterMix组成为:PCRbuffer(5×)4μl、MgCl21.5μl、Taq酶1.5μl、ddH2O4μl。
3.根据权利要求2所述的BRCA基因易感SNP位点检测组合物,其特征在于,所述BRCA基因易感SNP位点检测组合物的PCR反应条件包括:首先92~97℃预变性3~10分钟;然后聚合酶链式反应扩增阶段:92~97℃变性10~20s,50~65℃退火10~30s,70~75℃延伸10~20s,并进行10~15个循环。
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