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Clonal selection after gene therapy in sickle cell disease

While gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD), the occurrence of myeloid malignancies in clinical trials has prompted concern. To interrogate potential mechanisms underlying increased cancer risk, we used hematopoietic stem cell (HSC) clonal tracking by whole genome sequencing (WGS) to map the somatic mutation and clonal landscape of 2,592 gene modified as well as unmodified single stem and progenitor cells from six SCD patients undergoing gene therapy (7-26 years old, average 12.7× depth). Pre-GT phylogenetic trees in SCD were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified. However, an increased frequency of driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) were seen in both genetically modified and unmodified cells suggested positive selection of mutant clones during gene therapy. This work sheds light on the mutation landscape and HSC clonal dynamics in gene therapy for SCD and highlights enhanced fitness of some HSCs harboring pre-existing driver mutations following gene therapy. Future studies should define the long-term fate of mutant clones including any contribution to expansions associated with myeloid neoplasms.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001004620 Whole Genome Sequencing

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00008074513 cram 7.4 GB
EGAF00008074514 cram 8.7 GB
EGAF00008074515 cram 9.9 GB
EGAF00008074516 cram 7.8 GB
EGAF00008074517 cram 7.9 GB
EGAF00008074518 cram 8.7 GB
EGAF00008074519 cram 9.6 GB
EGAF00008074520 cram 7.1 GB
EGAF00008074521 cram 8.8 GB
EGAF00008074522 cram 9.2 GB
EGAF00008074523 cram 7.7 GB
EGAF00008074524 cram 7.3 GB
EGAF00008074525 cram 7.4 GB
EGAF00008074526 cram 7.8 GB
EGAF00008074527 cram 8.4 GB
EGAF00008074528 cram 8.3 GB
EGAF00008074529 cram 9.8 GB
EGAF00008074530 cram 9.0 GB
EGAF00008074531 cram 8.9 GB
EGAF00008074532 cram 8.3 GB
EGAF00008074533 cram 8.9 GB
EGAF00008074534 cram 8.9 GB
EGAF00008074535 cram 9.6 GB
EGAF00008074536 cram 10.0 GB
EGAF00008074537 cram 7.1 GB
EGAF00008074538 cram 8.4 GB
EGAF00008074539 cram 9.3 GB
EGAF00008074540 cram 7.1 GB
EGAF00008074541 cram 9.3 GB
EGAF00008074542 cram 9.0 GB
EGAF00008074543 cram 8.4 GB
EGAF00008074544 cram 8.2 GB
EGAF00008074545 cram 8.2 GB
EGAF00008074546 cram 7.7 GB
EGAF00008074547 cram 7.9 GB
EGAF00008074548 cram 8.8 GB
EGAF00008074549 cram 8.6 GB
EGAF00008074550 cram 9.5 GB
EGAF00008074551 cram 7.3 GB
EGAF00008074552 cram 8.6 GB
EGAF00008074553 cram 9.2 GB
EGAF00008074554 cram 8.9 GB
EGAF00008074555 cram 9.0 GB
EGAF00008074556 cram 8.3 GB
EGAF00008074557 cram 8.7 GB
EGAF00008074558 cram 8.8 GB
EGAF00008074559 cram 9.8 GB
EGAF00008074560 cram 8.9 GB
EGAF00008074561 cram 8.5 GB
EGAF00008074562 cram 9.1 GB
EGAF00008074563 cram 9.3 GB
EGAF00008074564 cram 8.3 GB
EGAF00008074565 cram 6.5 GB
EGAF00008074566 cram 7.5 GB
EGAF00008074567 cram 8.7 GB
EGAF00008074568 cram 8.4 GB
EGAF00008074569 cram 9.8 GB
EGAF00008074570 cram 10.1 GB
EGAF00008074571 cram 8.4 GB
EGAF00008074572 cram 10.4 GB
EGAF00008074573 cram 9.0 GB
EGAF00008074574 cram 9.3 GB
EGAF00008074575 cram 8.9 GB
EGAF00008074576 cram 10.4 GB
EGAF00008074577 cram 8.0 GB
EGAF00008074578 cram 7.1 GB
EGAF00008074579 cram 7.4 GB
EGAF00008074580 cram 8.2 GB
EGAF00008074581 cram 8.2 GB
EGAF00008074582 cram 7.4 GB
EGAF00008074583 cram 8.0 GB
EGAF00008074584 cram 8.6 GB
EGAF00008074585 cram 9.4 GB
EGAF00008074586 cram 9.0 GB
EGAF00008074587 cram 10.1 GB
EGAF00008074588 cram 8.3 GB
EGAF00008074589 cram 7.6 GB
EGAF00008074590 cram 6.7 GB
EGAF00008074591 cram 7.5 GB
EGAF00008074592 cram 7.5 GB
EGAF00008074593 cram 8.2 GB
EGAF00008074594 cram 7.4 GB
EGAF00008074595 cram 6.8 GB
EGAF00008074596 cram 9.5 GB
EGAF00008074597 cram 8.3 GB
EGAF00008074598 cram 7.8 GB
EGAF00008074599 cram 7.6 GB
EGAF00008074600 cram 7.9 GB
EGAF00008074601 cram 8.4 GB
EGAF00008074602 cram 8.0 GB
EGAF00008074603 cram 6.7 GB
EGAF00008074604 cram 8.6 GB
EGAF00008074605 cram 8.3 GB
EGAF00008074606 cram 7.4 GB
EGAF00008074607 cram 7.7 GB
EGAF00008074608 cram 6.9 GB
EGAF00008074609 cram 6.9 GB
EGAF00008074610 cram 8.6 GB
EGAF00008074611 cram 7.4 GB
EGAF00008074612 cram 6.6 GB
EGAF00008074613 cram 7.7 GB
EGAF00008074614 cram 8.4 GB
EGAF00008074615 cram 8.0 GB
EGAF00008074616 cram 8.4 GB
EGAF00008074617 cram 7.0 GB
EGAF00008074618 cram 7.4 GB
EGAF00008074619 cram 7.1 GB
EGAF00008074620 cram 7.4 GB
EGAF00008074621 cram 7.1 GB
EGAF00008074622 cram 6.6 GB
EGAF00008074623 cram 8.2 GB
EGAF00008074624 cram 8.2 GB
EGAF00008074625 cram 8.1 GB
EGAF00008074626 cram 7.8 GB
EGAF00008074627 cram 8.1 GB
EGAF00008074628 cram 7.6 GB
EGAF00008074629 cram 7.8 GB
EGAF00008074630 cram 7.7 GB
EGAF00008074631 cram 8.1 GB
EGAF00008074632 cram 7.4 GB
EGAF00008074633 cram 6.9 GB
EGAF00008074634 cram 8.0 GB
EGAF00008074635 cram 8.3 GB
EGAF00008074636 cram 7.3 GB
EGAF00008074637 cram 7.2 GB
EGAF00008074638 cram 6.4 GB
EGAF00008074639 cram 7.5 GB
EGAF00008074640 cram 7.5 GB
EGAF00008074641 cram 8.1 GB
EGAF00008074642 cram 7.9 GB
EGAF00008074643 cram 7.1 GB
EGAF00008074644 cram 7.9 GB
EGAF00008074645 cram 8.5 GB
EGAF00008074646 cram 6.9 GB
EGAF00008074647 cram 7.6 GB
EGAF00008074648 cram 7.4 GB
EGAF00008074649 cram 8.6 GB
EGAF00008074650 cram 7.8 GB
EGAF00008074651 cram 9.0 GB
EGAF00008074652 cram 8.2 GB
EGAF00008074653 cram 7.6 GB
EGAF00008074654 cram 6.4 GB
EGAF00008074655 cram 7.1 GB
EGAF00008074656 cram 7.5 GB
EGAF00008074657 cram 7.3 GB
EGAF00008074658 cram 9.3 GB
EGAF00008074659 cram 7.3 GB
EGAF00008074660 cram 8.8 GB
EGAF00008074661 cram 8.4 GB
EGAF00008074662 cram 7.3 GB
EGAF00008074663 cram 7.5 GB
EGAF00008074664 cram 7.5 GB
EGAF00008074665 cram 6.6 GB
EGAF00008074666 cram 6.8 GB
EGAF00008074667 cram 8.0 GB
EGAF00008074668 cram 8.3 GB
EGAF00008074669 cram 7.0 GB
EGAF00008074670 cram 7.6 GB
EGAF00008074671 cram 8.2 GB
EGAF00008074672 cram 8.0 GB
EGAF00008074673 cram 6.4 GB
EGAF00008074674 cram 7.0 GB
EGAF00008074675 cram 7.5 GB
EGAF00008074676 cram 7.4 GB
EGAF00008074677 cram 8.1 GB
EGAF00008074678 cram 9.6 GB
EGAF00008074679 cram 8.4 GB
EGAF00008074680 cram 7.2 GB
EGAF00008074681 cram 7.1 GB
EGAF00008074682 cram 7.5 GB
EGAF00008074683 cram 8.3 GB
EGAF00008074684 cram 7.2 GB
EGAF00008074685 cram 8.5 GB
EGAF00008074686 cram 9.0 GB
EGAF00008074687 cram 10.4 GB
EGAF00008074688 cram 7.9 GB
EGAF00008074689 cram 7.8 GB
EGAF00008074690 cram 8.4 GB
EGAF00008074691 cram 8.5 GB
EGAF00008074692 cram 9.3 GB
EGAF00008074693 cram 9.8 GB
EGAF00008074694 cram 9.6 GB
EGAF00008074695 cram 7.3 GB
EGAF00008074696 cram 7.3 GB
EGAF00008074697 cram 6.4 GB
EGAF00008074698 cram 8.9 GB
EGAF00008074699 cram 8.6 GB
EGAF00008074700 cram 9.7 GB
EGAF00008074701 cram 10.0 GB
EGAF00008074702 cram 8.3 GB
EGAF00008074703 cram 7.6 GB
EGAF00008074704 cram 8.2 GB
EGAF00008074705 cram 10.5 GB
EGAF00008074706 cram 8.5 GB
EGAF00008074707 cram 8.1 GB
EGAF00008074708 cram 7.8 GB
EGAF00008074709 cram 6.8 GB
EGAF00008074710 cram 7.9 GB
EGAF00008074711 cram 7.9 GB
EGAF00008074712 cram 7.9 GB
EGAF00008074713 cram 9.3 GB
EGAF00008074714 cram 8.7 GB
EGAF00008074715 cram 7.8 GB
EGAF00008074716 cram 5.8 GB
EGAF00008074717 cram 7.1 GB
EGAF00008074718 cram 8.5 GB
EGAF00008074719 cram 9.1 GB
EGAF00008074720 cram 8.1 GB
EGAF00008074721 cram 9.1 GB
EGAF00008074722 cram 6.9 GB
EGAF00008074723 cram 8.0 GB
EGAF00008074724 cram 7.8 GB
EGAF00008074725 cram 8.4 GB
EGAF00008074726 cram 6.9 GB
EGAF00008074727 cram 9.8 GB
EGAF00008074728 cram 8.0 GB
EGAF00008074729 cram 7.8 GB
EGAF00008074730 cram 8.9 GB
EGAF00008074731 cram 6.9 GB
EGAF00008074732 cram 8.2 GB
EGAF00008074733 cram 6.4 GB
EGAF00008074734 cram 8.7 GB
EGAF00008074735 cram 9.7 GB
EGAF00008074736 cram 7.1 GB
EGAF00008074737 cram 7.4 GB
EGAF00008074738 cram 7.3 GB
EGAF00008074739 cram 8.5 GB
EGAF00008074740 cram 7.9 GB
EGAF00008074741 cram 6.2 GB
EGAF00008074742 cram 8.2 GB
EGAF00008074743 cram 8.3 GB
EGAF00008074744 cram 8.0 GB
EGAF00008074745 cram 7.3 GB
EGAF00008074746 cram 9.4 GB
EGAF00008074747 cram 7.2 GB
EGAF00008074748 cram 6.2 GB
EGAF00008074749 cram 9.3 GB
EGAF00008074750 cram 8.7 GB
EGAF00008074751 cram 8.8 GB
EGAF00008074752 cram 7.4 GB
EGAF00008074753 cram 7.1 GB
EGAF00008074754 cram 8.0 GB
EGAF00008074755 cram 7.7 GB
EGAF00008074756 cram 7.9 GB
EGAF00008074757 cram 7.2 GB
EGAF00008074758 cram 7.4 GB
EGAF00008074759 cram 6.7 GB
EGAF00008074760 cram 7.9 GB
EGAF00008074761 cram 8.6 GB
EGAF00008074762 cram 7.4 GB
EGAF00008074763 cram 9.1 GB
EGAF00008074764 cram 7.3 GB
EGAF00008074765 cram 9.2 GB
EGAF00008074766 cram 7.0 GB
EGAF00008074767 cram 7.6 GB
EGAF00008074768 cram 8.9 GB
EGAF00008074769 cram 9.4 GB
EGAF00008074770 cram 7.3 GB
EGAF00008074771 cram 7.8 GB
EGAF00008074772 cram 8.7 GB
EGAF00008074773 cram 7.0 GB
EGAF00008074774 cram 6.6 GB
EGAF00008074775 cram 6.8 GB
EGAF00008074776 cram 7.8 GB
EGAF00008074777 cram 7.9 GB
EGAF00008074778 cram 6.8 GB
EGAF00008074779 cram 9.0 GB
EGAF00008074780 cram 8.4 GB
EGAF00008074781 cram 7.5 GB
EGAF00008074782 cram 6.9 GB
EGAF00008074783 cram 8.5 GB
EGAF00008074784 cram 7.1 GB
EGAF00008074785 cram 7.8 GB
EGAF00008074786 cram 9.0 GB
EGAF00008074787 cram 7.3 GB
EGAF00008074788 cram 8.6 GB
EGAF00008074789 cram 7.5 GB
EGAF00008074790 cram 8.1 GB
EGAF00008074791 cram 6.9 GB
EGAF00008074792 cram 6.2 GB
EGAF00008074793 cram 6.5 GB
EGAF00008074794 cram 7.7 GB
EGAF00008074795 cram 8.1 GB
EGAF00008074796 cram 8.5 GB
EGAF00008074797 cram 7.6 GB
EGAF00008074798 cram 8.0 GB
EGAF00008074799 cram 8.3 GB
EGAF00008074800 cram 7.4 GB
EGAF00008074801 cram 8.7 GB
EGAF00008074802 cram 8.3 GB
EGAF00008074803 cram 7.8 GB
EGAF00008074804 cram 7.3 GB
EGAF00008074805 cram 9.9 GB
EGAF00008074806 cram 8.2 GB
EGAF00008074807 cram 8.1 GB
EGAF00008074808 cram 7.9 GB
EGAF00008074809 cram 7.8 GB
EGAF00008074810 cram 8.5 GB
EGAF00008074811 cram 7.4 GB
EGAF00008074812 cram 8.3 GB
EGAF00008074813 cram 7.2 GB
EGAF00008074814 cram 8.3 GB
EGAF00008074815 cram 8.0 GB
EGAF00008074816 cram 8.0 GB
EGAF00008074817 cram 13.5 GB
EGAF00008074818 cram 7.9 GB
EGAF00008074819 cram 8.4 GB
EGAF00008074820 cram 7.1 GB
EGAF00008074821 cram 7.1 GB
EGAF00008074822 cram 9.3 GB
EGAF00008074823 cram 7.2 GB
EGAF00008074824 cram 8.4 GB
EGAF00008074825 cram 8.2 GB
EGAF00008074826 cram 7.4 GB
EGAF00008074827 cram 8.0 GB
EGAF00008074828 cram 9.1 GB
EGAF00008074829 cram 7.8 GB
EGAF00008074830 cram 6.3 GB
EGAF00008074831 cram 9.4 GB
EGAF00008074832 cram 7.0 GB
EGAF00008074833 cram 8.8 GB
EGAF00008074834 cram 7.3 GB
EGAF00008074835 cram 8.1 GB
EGAF00008074836 cram 6.7 GB
EGAF00008074837 cram 8.8 GB
EGAF00008074838 cram 7.3 GB
EGAF00008074839 cram 6.8 GB
EGAF00008074840 cram 9.1 GB
EGAF00008074841 cram 7.3 GB
EGAF00008074842 cram 8.0 GB
EGAF00008074843 cram 7.3 GB
EGAF00008074844 cram 8.4 GB
EGAF00008074845 cram 7.2 GB
EGAF00008074846 cram 7.6 GB
EGAF00008074847 cram 9.0 GB
EGAF00008074848 cram 8.1 GB
EGAF00008074849 cram 7.6 GB
EGAF00008074850 cram 8.0 GB
EGAF00008074851 cram 7.9 GB
EGAF00008074852 cram 9.0 GB
EGAF00008074853 cram 8.0 GB
EGAF00008074854 cram 8.1 GB
EGAF00008074855 cram 7.0 GB
EGAF00008074856 cram 7.3 GB
EGAF00008074857 cram 8.3 GB
EGAF00008074858 cram 7.9 GB
EGAF00008074859 cram 8.0 GB
EGAF00008074860 cram 7.3 GB
EGAF00008074861 cram 8.8 GB
EGAF00008074862 cram 9.7 GB
EGAF00008074863 cram 7.7 GB
EGAF00008074864 cram 7.1 GB
EGAF00008074865 cram 7.6 GB
EGAF00008074866 cram 9.3 GB
EGAF00008074867 cram 8.6 GB
EGAF00008074868 cram 7.6 GB
EGAF00008074869 cram 7.7 GB
EGAF00008074870 cram 7.0 GB
EGAF00008074871 cram 9.2 GB
EGAF00008074872 cram 8.2 GB
EGAF00008074873 cram 8.5 GB
EGAF00008074874 cram 8.8 GB
EGAF00008074875 cram 8.2 GB
EGAF00008074876 cram 9.4 GB
EGAF00008074877 cram 8.0 GB
EGAF00008074878 cram 9.4 GB
EGAF00008074879 cram 9.0 GB
EGAF00008074880 cram 8.6 GB
EGAF00008074881 cram 7.4 GB
EGAF00008074882 cram 9.2 GB
EGAF00008074883 cram 9.2 GB
EGAF00008074884 cram 7.9 GB
EGAF00008074885 cram 9.4 GB
EGAF00008074886 cram 6.5 GB
EGAF00008074887 cram 7.9 GB
EGAF00008074888 cram 9.3 GB
EGAF00008074889 cram 12.4 GB
EGAF00008074890 cram 12.9 GB
EGAF00008074891 cram 11.3 GB
EGAF00008074892 cram 14.4 GB
EGAF00008074893 cram 13.2 GB
EGAF00008074894 cram 10.9 GB
EGAF00008074895 cram 12.9 GB
EGAF00008074896 cram 13.1 GB
EGAF00008074897 cram 12.0 GB
EGAF00008074898 cram 13.3 GB
EGAF00008074899 cram 12.1 GB
EGAF00008074900 cram 12.0 GB
EGAF00008074901 cram 14.1 GB
EGAF00008074902 cram 11.6 GB
EGAF00008074903 cram 12.1 GB
EGAF00008074904 cram 12.8 GB
EGAF00008074905 cram 13.7 GB
EGAF00008074906 cram 12.3 GB
EGAF00008074907 cram 15.5 GB
EGAF00008074908 cram 13.5 GB
EGAF00008074909 cram 6.5 GB
EGAF00008074910 cram 12.8 GB
EGAF00008074911 cram 14.4 GB
EGAF00008074912 cram 12.2 GB
EGAF00008074913 cram 11.8 GB
EGAF00008074914 cram 9.9 GB
EGAF00008074915 cram 9.3 GB
EGAF00008074916 cram 8.3 GB
EGAF00008074917 cram 8.1 GB
EGAF00008074918 cram 8.3 GB
EGAF00008074919 cram 9.2 GB
EGAF00008074920 cram 7.7 GB
EGAF00008074921 cram 10.5 GB
EGAF00008074922 cram 8.8 GB
EGAF00008074923 cram 9.7 GB
EGAF00008074924 cram 7.9 GB
EGAF00008074925 cram 8.6 GB
EGAF00008074926 cram 7.4 GB
EGAF00008074927 cram 7.0 GB
EGAF00008074928 cram 8.6 GB
EGAF00008074929 cram 9.2 GB
EGAF00008074930 cram 10.1 GB
EGAF00008074931 cram 9.8 GB
EGAF00008074932 cram 7.1 GB
EGAF00008074933 cram 7.2 GB
EGAF00008074934 cram 7.2 GB
EGAF00008074935 cram 9.0 GB
EGAF00008074936 cram 7.5 GB
EGAF00008074937 cram 7.5 GB
EGAF00008074938 cram 11.6 GB
EGAF00008074939 cram 7.9 GB
EGAF00008074940 cram 7.9 GB
EGAF00008074941 cram 11.1 GB
EGAF00008074942 cram 8.2 GB
EGAF00008074943 cram 7.1 GB
EGAF00008074944 cram 7.1 GB
EGAF00008074945 cram 7.1 GB
EGAF00008074946 cram 8.6 GB
EGAF00008074947 cram 7.7 GB
EGAF00008074948 cram 7.0 GB
EGAF00008074949 cram 8.3 GB
EGAF00008074950 cram 7.9 GB
EGAF00008074951 cram 8.0 GB
EGAF00008074952 cram 9.0 GB
EGAF00008074953 cram 7.6 GB
EGAF00008074954 cram 8.3 GB
EGAF00008074955 cram 9.2 GB
EGAF00008074956 cram 9.2 GB
EGAF00008074957 cram 9.0 GB
EGAF00008074958 cram 9.2 GB
EGAF00008074959 cram 8.5 GB
EGAF00008074960 cram 9.0 GB
EGAF00008074961 cram 8.8 GB
EGAF00008074962 cram 8.4 GB
EGAF00008074963 cram 7.7 GB
EGAF00008074964 cram 8.7 GB
EGAF00008074965 cram 8.8 GB
EGAF00008074966 cram 7.5 GB
EGAF00008074967 cram 8.6 GB
EGAF00008074968 cram 7.9 GB
EGAF00008074969 cram 8.5 GB
EGAF00008074970 cram 8.9 GB
EGAF00008074971 cram 9.0 GB
EGAF00008074972 cram 9.0 GB
EGAF00008074973 cram 8.5 GB
EGAF00008074974 cram 9.3 GB
EGAF00008074975 cram 7.7 GB
EGAF00008074976 cram 9.0 GB
EGAF00008074977 cram 8.9 GB
EGAF00008074978 cram 7.4 GB
EGAF00008074979 cram 7.8 GB
EGAF00008074980 cram 8.7 GB
EGAF00008074981 cram 7.4 GB
EGAF00008074982 cram 9.2 GB
EGAF00008074983 cram 9.1 GB
EGAF00008074984 cram 10.0 GB
EGAF00008074985 cram 8.6 GB
EGAF00008074986 cram 7.9 GB
EGAF00008074987 cram 8.5 GB
EGAF00008074988 cram 8.2 GB
EGAF00008074989 cram 6.5 GB
EGAF00008074990 cram 9.3 GB
EGAF00008074991 cram 8.4 GB
EGAF00008074992 cram 8.8 GB
EGAF00008074993 cram 7.0 GB
EGAF00008074994 cram 8.3 GB
EGAF00008074995 cram 8.0 GB
EGAF00008074996 cram 7.5 GB
EGAF00008074997 cram 9.4 GB
EGAF00008074998 cram 8.1 GB
EGAF00008074999 cram 8.5 GB
EGAF00008075000 cram 7.5 GB
EGAF00008075001 cram 9.0 GB
EGAF00008075002 cram 9.8 GB
EGAF00008075003 cram 9.2 GB
EGAF00008075004 cram 9.4 GB
EGAF00008075005 cram 8.2 GB
EGAF00008075006 cram 8.5 GB
EGAF00008075007 cram 6.7 GB
EGAF00008075008 cram 7.7 GB
EGAF00008075009 cram 6.9 GB
EGAF00008075010 cram 8.2 GB
EGAF00008075011 cram 8.2 GB
EGAF00008075012 cram 6.5 GB
EGAF00008075013 cram 8.2 GB
EGAF00008075014 cram 9.6 GB
EGAF00008075015 cram 8.1 GB
EGAF00008075016 cram 6.7 GB
EGAF00008075017 cram 8.0 GB
EGAF00008075018 cram 7.0 GB
EGAF00008075019 cram 7.5 GB
EGAF00008075020 cram 7.9 GB
EGAF00008075021 cram 6.4 GB
EGAF00008075022 cram 6.8 GB
EGAF00008075023 cram 7.9 GB
EGAF00008075024 cram 7.7 GB
EGAF00008075025 cram 8.2 GB
EGAF00008075026 cram 7.0 GB
EGAF00008075027 cram 7.4 GB
EGAF00008075028 cram 8.2 GB
EGAF00008075029 cram 7.6 GB
EGAF00008075030 cram 7.4 GB
EGAF00008075031 cram 6.5 GB
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EGAF00008075066 cram 11.0 GB
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EGAF00008075091 cram 10.3 GB
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EGAF00008075126 cram 8.7 GB
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EGAF00008075493 cram 11.1 GB
EGAF00008075494 cram 16.2 GB
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EGAF00008075497 cram 4.8 GB
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EGAF00008075503 cram 6.9 GB
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EGAF00008075507 cram 8.8 GB
EGAF00008075508 cram 9.5 GB
EGAF00008075509 cram 8.7 GB
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EGAF00008075512 cram 7.3 GB
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EGAF00008075515 cram 7.0 GB
EGAF00008075516 cram 8.5 GB
EGAF00008075517 cram 7.8 GB
EGAF00008075518 cram 6.9 GB
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EGAF00008075520 cram 7.1 GB
EGAF00008075521 cram 9.7 GB
EGAF00008075522 cram 9.6 GB
EGAF00008075523 cram 7.0 GB
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EGAF00008075527 cram 8.7 GB
EGAF00008075528 cram 8.0 GB
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EGAF00008075531 cram 5.7 GB
EGAF00008075532 cram 8.3 GB
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EGAF00008075534 cram 7.7 GB
EGAF00008075535 cram 12.5 GB
EGAF00008075536 cram 7.5 GB
EGAF00008075537 cram 6.2 GB
EGAF00008075538 cram 15.6 GB
EGAF00008075539 cram 8.0 GB
EGAF00008075540 cram 9.0 GB
EGAF00008075541 cram 6.6 GB
EGAF00008075542 cram 7.8 GB
EGAF00008075543 cram 6.4 GB
EGAF00008075544 cram 7.1 GB
EGAF00008075545 cram 6.0 GB
EGAF00008075546 cram 7.9 GB
EGAF00008075547 cram 7.3 GB
EGAF00008075548 cram 6.7 GB
EGAF00008075549 cram 7.5 GB
EGAF00008075550 cram 6.4 GB
EGAF00008075551 cram 7.3 GB
EGAF00008075552 cram 7.0 GB
EGAF00008075553 cram 8.1 GB
EGAF00008075554 cram 8.6 GB
EGAF00008075555 cram 6.5 GB
EGAF00008075556 cram 7.6 GB
EGAF00008075557 cram 6.2 GB
EGAF00008075558 cram 8.7 GB
EGAF00008075559 cram 8.3 GB
EGAF00008075560 cram 6.2 GB
EGAF00008075561 cram 6.0 GB
EGAF00008075574 cram 7.0 GB
EGAF00008075575 cram 7.9 GB
EGAF00008075576 cram 8.3 GB
EGAF00008075577 cram 7.6 GB
EGAF00008075578 cram 9.7 GB
EGAF00008075579 cram 8.9 GB
EGAF00008075580 cram 6.3 GB
EGAF00008075581 cram 7.5 GB
EGAF00008075582 cram 7.7 GB
EGAF00008075583 cram 6.4 GB
EGAF00008075584 cram 6.8 GB
EGAF00008075585 cram 7.7 GB
EGAF00008075586 cram 7.0 GB
EGAF00008075587 cram 7.9 GB
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EGAF00008076055 cram 1.7 GB
EGAF00008076056 cram 1.6 GB
EGAF00008076057 cram 2.0 GB
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EGAF00008076060 cram 1.8 GB
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EGAF00008076067 cram 1.6 GB
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EGAF00008076074 cram 1.8 GB
EGAF00008076075 cram 1.7 GB
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EGAF00008076079 cram 1.6 GB
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EGAF00008076082 cram 1.7 GB
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EGAF00008076087 cram 1.6 GB
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EGAF00008076090 cram 1.7 GB
EGAF00008076091 cram 1.6 GB
EGAF00008076092 cram 1.5 GB
EGAF00008076093 cram 1.7 GB
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EGAF00008076095 cram 1.8 GB
EGAF00008076096 cram 1.7 GB
EGAF00008076097 cram 1.5 GB
EGAF00008076098 cram 1.7 GB
EGAF00008076099 cram 1.6 GB
EGAF00008076100 cram 1.1 GB
EGAF00008076101 cram 1.5 GB
EGAF00008076102 cram 1.9 GB
EGAF00008076103 cram 1.4 GB
EGAF00008076104 cram 1.6 GB
EGAF00008076105 cram 1.2 GB
EGAF00008076106 cram 1.5 GB
EGAF00008076107 cram 1.5 GB
EGAF00008076108 cram 1.6 GB
EGAF00008076109 cram 1.2 GB
EGAF00008076110 cram 1.4 GB
EGAF00008076111 cram 1.3 GB
EGAF00008076112 cram 1.5 GB
EGAF00008076113 cram 1.7 GB
EGAF00008076114 cram 1.6 GB
EGAF00008076115 cram 1.7 GB
EGAF00008076116 cram 1.6 GB
EGAF00008076117 cram 2.3 GB
EGAF00008076118 cram 1.8 GB
EGAF00008076119 cram 1.2 GB
EGAF00008076120 cram 1.8 GB
EGAF00008076121 cram 2.5 GB
EGAF00008076122 cram 1.7 GB
EGAF00008076123 cram 1.6 GB
EGAF00008076124 cram 2.0 GB
EGAF00008076125 cram 2.7 GB
EGAF00008076126 cram 7.5 GB
EGAF00008076127 cram 4.5 GB
EGAF00008076128 cram 5.7 GB
EGAF00008076129 cram 5.6 GB
EGAF00008076130 cram 5.8 GB
EGAF00008076131 cram 6.1 GB
EGAF00008076132 cram 6.3 GB
EGAF00008076133 cram 6.5 GB
EGAF00008076134 cram 4.8 GB
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EGAF00008076137 cram 6.6 GB
EGAF00008076138 cram 5.6 GB
EGAF00008076139 cram 6.5 GB
EGAF00008076140 cram 5.6 GB
EGAF00008076141 cram 5.1 GB
EGAF00008076142 cram 6.2 GB
EGAF00008076143 cram 7.0 GB
EGAF00008076144 cram 4.6 GB
EGAF00008076145 cram 6.1 GB
EGAF00008076146 cram 6.1 GB
EGAF00008076147 cram 6.2 GB
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EGAF00008076157 cram 1.7 GB
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EGAF00008076161 cram 1.6 GB
EGAF00008076162 cram 1.7 GB
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EGAF00008076168 cram 1.6 GB
EGAF00008076169 cram 1.9 GB
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EGAF00008076188 cram 1.7 GB
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EGAF00008076219 cram 1.8 GB
EGAF00008076220 cram 1.6 GB
EGAF00008076221 cram 1.7 GB
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EGAF00008076223 cram 1.3 GB
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EGAF00008076226 cram 1.6 GB
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EGAF00008076228 cram 1.8 GB
EGAF00008076229 cram 1.7 GB
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EGAF00008076232 cram 1.6 GB
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EGAF00008076303 cram 2.8 GB
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EGAF00008076597 cram 5.9 GB
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EGAF00008076632 cram 1.9 GB
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EGAF00008076637 cram 1.7 GB
EGAF00008076638 cram 1.7 GB
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EGAF00008076644 cram 1.7 GB
EGAF00008076645 cram 1.9 GB
EGAF00008076646 cram 1.8 GB
EGAF00008076647 cram 1.5 GB
EGAF00008076648 cram 1.6 GB
EGAF00008076649 cram 2.0 GB
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EGAF00008076651 cram 1.8 GB
EGAF00008076652 cram 1.5 GB
EGAF00008076653 cram 1.7 GB
EGAF00008076654 cram 1.9 GB
EGAF00008076655 cram 2.2 GB
EGAF00008076656 cram 1.6 GB
EGAF00008076657 cram 1.7 GB
EGAF00008076658 cram 1.5 GB
EGAF00008076659 cram 1.6 GB
EGAF00008076660 cram 1.6 GB
EGAF00008076661 cram 2.3 GB
EGAF00008076662 cram 1.8 GB
EGAF00008076663 cram 1.6 GB
EGAF00008076664 cram 1.4 GB
EGAF00008076665 cram 1.7 GB
EGAF00008076666 cram 1.8 GB
EGAF00008076667 cram 1.9 GB
EGAF00008076668 cram 1.8 GB
EGAF00008076669 cram 1.8 GB
EGAF00008076670 cram 2.0 GB
EGAF00008076671 cram 2.4 GB
EGAF00008076672 cram 1.9 GB
EGAF00008076673 cram 2.0 GB
EGAF00008076674 cram 2.1 GB
EGAF00008076675 cram 1.5 GB
EGAF00008076676 cram 1.7 GB
EGAF00008076677 cram 1.8 GB
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EGAF00008076709 cram 988.6 MB
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EGAF00008077147 cram 9.3 GB
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EGAF00008077151 cram 6.6 GB
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EGAF00008077153 cram 6.0 GB
EGAF00008077154 cram 5.0 GB
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EGAF00008077157 cram 5.8 GB
EGAF00008077158 cram 8.0 GB
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EGAF00008077160 cram 6.7 GB
EGAF00008077161 cram 7.3 GB
EGAF00008077162 cram 6.3 GB
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EGAF00008077165 cram 6.4 GB
EGAF00008077166 cram 6.1 GB
EGAF00008077167 cram 5.5 GB
EGAF00008077168 cram 6.8 GB
EGAF00008077169 cram 4.0 GB
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EGAF00008077171 cram 6.7 GB
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EGAF00008077173 cram 4.1 GB
EGAF00008077174 cram 7.8 GB
EGAF00008077175 cram 5.8 GB
EGAF00008077176 cram 6.9 GB
EGAF00008077177 cram 7.3 GB
EGAF00008077178 cram 7.2 GB
EGAF00008077179 cram 6.8 GB
EGAF00008077180 cram 5.2 GB
EGAF00008077181 cram 4.7 GB
EGAF00008077182 cram 6.2 GB
EGAF00008077183 cram 6.1 GB
EGAF00008077184 cram 5.7 GB
EGAF00008077185 cram 7.7 GB
EGAF00008077186 cram 7.1 GB
EGAF00008077187 cram 6.4 GB
EGAF00008077188 cram 5.9 GB
EGAF00008077189 cram 6.2 GB
EGAF00008077190 cram 5.3 GB
EGAF00008077191 cram 7.2 GB
EGAF00008077192 cram 6.6 GB
EGAF00008077193 cram 7.5 GB
EGAF00008077194 cram 6.5 GB
EGAF00008077195 cram 7.0 GB
EGAF00008077196 cram 6.3 GB
EGAF00008077197 cram 7.0 GB
EGAF00008077198 cram 6.4 GB
EGAF00008077199 cram 7.2 GB
EGAF00008077200 cram 6.0 GB
EGAF00008077201 cram 6.1 GB
EGAF00008077202 cram 5.8 GB
EGAF00008077203 cram 6.5 GB
EGAF00008077204 cram 7.9 GB
EGAF00008077205 cram 5.9 GB
EGAF00008077206 cram 6.9 GB
EGAF00008077207 cram 5.1 GB
EGAF00008077208 cram 5.5 GB
EGAF00008077209 cram 6.5 GB
EGAF00008077210 cram 6.7 GB
EGAF00008077211 cram 5.9 GB
EGAF00008077212 cram 6.7 GB
EGAF00008077213 cram 8.1 GB
EGAF00008077214 cram 8.4 GB
EGAF00008077215 cram 7.0 GB
EGAF00008077216 cram 5.6 GB
EGAF00008077217 cram 6.6 GB
EGAF00008077218 cram 6.6 GB
EGAF00008077219 cram 5.4 GB
EGAF00008077220 cram 6.7 GB
EGAF00008077221 cram 8.6 GB
EGAF00008077222 cram 7.0 GB
EGAF00008077223 cram 6.6 GB
EGAF00008077224 cram 4.5 GB
EGAF00008077225 cram 5.6 GB
EGAF00008077226 cram 6.4 GB
EGAF00008077227 cram 6.5 GB
EGAF00008077228 cram 6.3 GB
EGAF00008077229 cram 5.5 GB
EGAF00008077230 cram 6.2 GB
EGAF00008077231 cram 5.9 GB
EGAF00008077232 cram 6.4 GB
EGAF00008077233 cram 7.0 GB
EGAF00008077234 cram 7.1 GB
EGAF00008077235 cram 9.2 GB
EGAF00008077236 cram 9.2 GB
EGAF00008077237 cram 5.0 GB
EGAF00008077238 cram 7.4 GB
EGAF00008077239 cram 6.3 GB
EGAF00008077240 cram 5.2 GB
EGAF00008077241 cram 2.6 GB
EGAF00008077242 cram 1.9 GB
EGAF00008077243 cram 2.3 GB
EGAF00008077244 cram 1.9 GB
EGAF00008077245 cram 1.9 GB
EGAF00008077246 cram 1.6 GB
EGAF00008077247 cram 1.7 GB
EGAF00008077248 cram 1.5 GB
EGAF00008077249 cram 1.0 GB
EGAF00008077250 cram 1.7 GB
EGAF00008077251 cram 1.6 GB
EGAF00008077252 cram 2.2 GB
EGAF00008077253 cram 2.0 GB
EGAF00008077254 cram 1.8 GB
EGAF00008077255 cram 2.0 GB
EGAF00008077256 cram 1.9 GB
EGAF00008077257 cram 1.3 GB
EGAF00008077258 cram 1.7 GB
EGAF00008077259 cram 1.8 GB
EGAF00008077260 cram 1.7 GB
EGAF00008077261 cram 1.5 GB
EGAF00008077262 cram 1.8 GB
EGAF00008077263 cram 1.1 GB
EGAF00008077264 cram 2.1 GB
EGAF00008077265 cram 1.8 GB
EGAF00008077266 cram 1.2 GB
EGAF00008077267 cram 1.1 GB
EGAF00008077268 cram 2.2 GB
EGAF00008077269 cram 1.6 GB
EGAF00008077270 cram 1.9 GB
EGAF00008077271 cram 2.0 GB
EGAF00008077272 cram 2.1 GB
EGAF00008077273 cram 1.9 GB
EGAF00008077274 cram 1.5 GB
EGAF00008077275 cram 1.3 GB
EGAF00008077276 cram 1.8 GB
EGAF00008077277 cram 1.8 GB
EGAF00008077278 cram 1.6 GB
EGAF00008077279 cram 2.2 GB
EGAF00008077280 cram 2.0 GB
EGAF00008077281 cram 1.8 GB
EGAF00008077282 cram 1.6 GB
EGAF00008077283 cram 1.7 GB
EGAF00008077284 cram 1.5 GB
EGAF00008077285 cram 2.0 GB
EGAF00008077286 cram 1.8 GB
EGAF00008077287 cram 2.1 GB
EGAF00008077288 cram 1.8 GB
EGAF00008077289 cram 2.0 GB
EGAF00008077290 cram 1.7 GB
EGAF00008077291 cram 2.0 GB
EGAF00008077292 cram 1.8 GB
EGAF00008077293 cram 2.1 GB
EGAF00008077294 cram 1.7 GB
EGAF00008077295 cram 1.7 GB
EGAF00008077296 cram 1.6 GB
EGAF00008077297 cram 1.7 GB
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EGAF00008077299 cram 1.7 GB
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EGAF00008077301 cram 1.4 GB
EGAF00008077302 cram 1.5 GB
EGAF00008077303 cram 1.8 GB
EGAF00008077304 cram 1.9 GB
EGAF00008077305 cram 1.7 GB
EGAF00008077306 cram 1.8 GB
EGAF00008077307 cram 2.3 GB
EGAF00008077308 cram 2.4 GB
EGAF00008077309 cram 2.0 GB
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EGAF00008077311 cram 1.8 GB
EGAF00008077312 cram 1.8 GB
EGAF00008077313 cram 1.5 GB
EGAF00008077314 cram 1.9 GB
EGAF00008077315 cram 2.3 GB
EGAF00008077316 cram 2.0 GB
EGAF00008077317 cram 1.8 GB
EGAF00008077318 cram 1.2 GB
EGAF00008077319 cram 1.6 GB
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EGAF00008077321 cram 1.8 GB
EGAF00008077322 cram 1.8 GB
EGAF00008077323 cram 1.6 GB
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EGAF00008077325 cram 1.7 GB
EGAF00008077326 cram 1.8 GB
EGAF00008077327 cram 1.9 GB
EGAF00008077328 cram 1.9 GB
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EGAF00008077330 cram 2.6 GB
EGAF00008077331 cram 1.4 GB
EGAF00008077332 cram 2.1 GB
EGAF00008077333 cram 1.8 GB
EGAF00008077334 cram 1.5 GB
EGAF00008077335 cram 2.2 GB
EGAF00008077336 cram 1.6 GB
EGAF00008077337 cram 1.7 GB
EGAF00008077338 cram 1.8 GB
EGAF00008077339 cram 1.8 GB
EGAF00008077340 cram 1.8 GB
EGAF00008077341 cram 1.8 GB
EGAF00008077342 cram 2.1 GB
EGAF00008077343 cram 1.7 GB
EGAF00008077344 cram 1.7 GB
EGAF00008077345 cram 1.7 GB
EGAF00008077346 cram 1.6 GB
EGAF00008077347 cram 1.9 GB
EGAF00008077348 cram 1.6 GB
EGAF00008077349 cram 1.8 GB
EGAF00008077350 cram 1.7 GB
EGAF00008077351 cram 2.0 GB
EGAF00008077352 cram 1.5 GB
EGAF00008077353 cram 1.8 GB
EGAF00008077354 cram 2.1 GB
EGAF00008077355 cram 1.7 GB
EGAF00008077356 cram 1.8 GB
EGAF00008077357 cram 1.7 GB
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EGAF00008077361 cram 1.7 GB
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EGAF00008077364 cram 1.3 GB
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EGAF00008077366 cram 1.9 GB
EGAF00008077367 cram 2.1 GB
EGAF00008077368 cram 1.6 GB
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EGAF00008077371 cram 1.6 GB
EGAF00008077372 cram 1.7 GB
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EGAF00008077383 cram 1.8 GB
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EGAF00008077387 cram 1.6 GB
EGAF00008077388 cram 2.1 GB
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EGAF00008077390 cram 1.6 GB
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EGAF00008077392 cram 2.3 GB
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EGAF00008077400 cram 1.9 GB
EGAF00008077401 cram 2.3 GB
EGAF00008077402 cram 1.7 GB
EGAF00008077403 cram 1.6 GB
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EGAF00008077407 cram 1.7 GB
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EGAF00008077433 cram 2.2 GB
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EGAF00008077545 cram 2.2 GB
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EGAF00008077550 cram 1.9 GB
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EGAF00008077568 cram 1.9 GB
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EGAF00008077574 cram 1.9 GB
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EGAF00008077577 cram 2.3 GB
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EGAF00008077581 cram 2.7 GB
EGAF00008077582 cram 1.9 GB
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EGAF00008077584 cram 2.3 GB
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EGAF00008077586 cram 2.8 GB
EGAF00008077587 cram 1.6 GB
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EGAF00008077590 cram 2.8 GB
EGAF00008077591 cram 2.4 GB
EGAF00008077592 cram 2.3 GB
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EGAF00008077594 cram 2.8 GB
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EGAF00008077597 cram 2.6 GB
EGAF00008077598 cram 2.0 GB
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EGAF00008077608 cram 2.6 GB
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EGAF00008077618 cram 2.7 GB
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EGAF00008077638 cram 2.6 GB
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EGAF00008077642 cram 2.3 GB
EGAF00008077643 cram 1.9 GB
EGAF00008077644 cram 2.7 GB
EGAF00008077645 cram 2.2 GB
EGAF00008077646 cram 2.7 GB
EGAF00008077647 cram 1.9 GB
EGAF00008077648 cram 2.6 GB
EGAF00008077649 cram 2.4 GB
EGAF00008077650 cram 2.1 GB
EGAF00008077651 cram 2.8 GB
EGAF00008077652 cram 1.6 GB
EGAF00008077653 cram 2.5 GB
EGAF00008077654 cram 2.5 GB
EGAF00008077655 cram 2.8 GB
EGAF00008077656 cram 2.5 GB
EGAF00008077657 cram 2.3 GB
EGAF00008077658 cram 2.2 GB
EGAF00008077659 cram 2.8 GB
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EGAF00008077661 cram 2.8 GB
EGAF00008077662 cram 2.7 GB
EGAF00008077663 cram 2.0 GB
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EGAF00008077665 cram 2.8 GB
EGAF00008077666 cram 2.4 GB
EGAF00008077667 cram 2.2 GB
EGAF00008077668 cram 2.5 GB
EGAF00008077669 cram 2.4 GB
EGAF00008077670 cram 2.5 GB
EGAF00008077671 cram 2.3 GB
EGAF00008077672 cram 2.6 GB
EGAF00008077673 cram 2.6 GB
EGAF00008077674 cram 2.4 GB
EGAF00008077675 cram 2.3 GB
EGAF00008077676 cram 2.6 GB
EGAF00008077677 cram 2.6 GB
EGAF00