Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia by Stella T. Chou, Jonathan M. Flanagan, Sunitha.

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Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia by Stella T. Chou, Jonathan M. Flanagan, Sunitha Vege, Naomi L. C. Luban, R. Clark Brown, Russell E. Ware, and Connie M. Westhoff BloodAdv Volume 1(18):1414-1422 August 8, 2017 © 2017 by The American Society of Hematology

Stella T. Chou et al. Blood Adv 2017;1:1414-1422 © 2017 by The American Society of Hematology

Anti-Rh and anti-K in SWiTCH patients at trial enrollment. Anti-Rh and anti-K in SWiTCH patients at trial enrollment. (A) The number and specificity of antibodies identified in 27 patients who are either negative or positive for the corresponding antigen by serologic testing. (B) The number of patients with partial Rh antigens (and no corresponding conventional allele) determined by high-resolution RH genotyping and at risk of alloantibody (n = 27 Rh alloimmunized and 27 non-alloimmunized at enrollment). Stella T. Chou et al. Blood Adv 2017;1:1414-1422 © 2017 by The American Society of Hematology

Mercury analysis pipeline. Mercury analysis pipeline. (A) Raw data from the sequencing instrument is passed to primary analysis software to generate sequence reads and base call confidence values (qualities). (B) Reads and qualities are passed along to a mapping tool Burrows-Wheeler algorithm (BWA) for comparison with a reference genome. The placement of reads on the reference genome produces a Binary-format Sequence Alignment Map (BAM) file and individual event BAMs were merged to make a single sample-level BAM file. (C) AtlasSNP and Genome Analysis Toolkit (GATK) are used to identify variants and produce annotated variant call files (VCFs). (D) In this study, we specifically interrogated WES data for the RHD and RHCE genes compared with conventional targeted assays. Stella T. Chou et al. Blood Adv 2017;1:1414-1422 © 2017 by The American Society of Hematology

WES coverage for RHD and RHCE genes. WES coverage for RHD and RHCE genes. (A) The median number of individual sequence reads are given for each polymorphism identified by exome sequencing. The sequence reads were aligned to the human reference sequence GRCh37, and median coverage was calculated for the entire SWiTCH cohort (n = 134). All exons (rectangles) had greater than 10× median coverage except RHD exon 8 (marked in red). (B) Normalized sequence read depth for RHCE exons 1, 2, and 3 (n = 54). Individuals with RHCE*Ce have a reduced ratio for exon 2 compared with exons 1 and 3 (orange bar). (C) Normalized sequence read depth for RHD, RHCE, and neighboring genes (n = 54). Genes with 2 copies are indicated as black bars, 1 copy as orange bars, and no copies as red bars. Stella T. Chou et al. Blood Adv 2017;1:1414-1422 © 2017 by The American Society of Hematology