NATURE GENETICS CORRECTION NOTICE Nat. Genet. 49, 238–248 (2017) SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome Natalie D Shaw, Harrison Brand, Zachary A Kupchinsky, Hemant Bengani, Lacey Plummer, Takako I Jones, Serkan Erdin, Kathleen A Williamson, Joe Rainger, Alexei Stortchevoi, Kaitlin Samocha, Benjamin B Currall, Donncha S Dunican, Ryan L Collins, Jason R Willer, Angela Lek, Monkol Lek, Malik Nassan, Shahrin Pereira, Tammy Kammin, Diane Lucente, Alexandra Silva, Catarina M Seabra, Colby Chiang, Yu An, Morad Ansari, Jacqueline K Rainger, Shelagh Joss, Jill Clayton Smith, Margaret F Lippincott, Sylvia S Singh, Nirav Patel, Jenny W Jing, Jennifer R Law, Nalton Ferraro, Alain Verloes, Anita Rauch, Katharina Steindl, Markus Zweier, Ianina Scheer, Daisuke Sato, Nobuhiko Okamoto, Christina Jacobsen, Jeanie Tryggestad, Steven Chernausek, Lisa A Schimmenti, Benjamin Brasseur, Claudia Cesaretti, Jose E García-Ortiz, Tatiana Pineda Buitrago, Orlando Perez Silva, Jodi D Hoffman, Wolfgang Mühlbauer, Klaus W Ruprecht, Bart L Loeys, Masato Shino, Angela M Kaindl, Chie-Hee Cho, Cynthia C Morton, Richard R Meehan, Veronica van Heyningen, Eric C Liao, Ravikumar Balasubramanian, Janet E Hall, Stephanie B Seminara, Daniel Macarthur, Steven A Moore, Koh-ichiro Yoshiura, James F Gusella, Joseph A Marsh, John M Graham Jr, Angela E Lin, Nicholas Katsanis, Peter L Jones, William F Crowley Jr, Erica E Davis, David R FitzPatrick & Michael E Talkowski In the supplementary information originally posted online, conversion errors introduced during the production of the PDF of supplementary figures corrupted some of the text in Supplementary Figure 1, the figure legend for Supplementary Figure 3 and Supplementary Figure 9. The errors have been corrected in this file as of 20 March 2017.
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NATURE GENETICS
CORRECT ION NOT ICE
Nat. Genet. 49, 238–248 (2017)
SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndromeNatalie D Shaw, Harrison Brand, Zachary A Kupchinsky, Hemant Bengani, Lacey Plummer, Takako I Jones, Serkan Erdin, Kathleen A Williamson, Joe Rainger, Alexei Stortchevoi, Kaitlin Samocha, Benjamin B Currall, Donncha S Dunican, Ryan L Collins, Jason R Willer, Angela Lek, Monkol Lek, Malik Nassan, Shahrin Pereira, Tammy Kammin, Diane Lucente, Alexandra Silva, Catarina M Seabra, Colby Chiang, Yu An, Morad Ansari, Jacqueline K Rainger, Shelagh Joss, Jill Clayton Smith, Margaret F Lippincott, Sylvia S Singh, Nirav Patel, Jenny W Jing, Jennifer R Law, Nalton Ferraro, Alain Verloes, Anita Rauch, Katharina Steindl, Markus Zweier, Ianina Scheer, Daisuke Sato, Nobuhiko Okamoto, Christina Jacobsen, Jeanie Tryggestad, Steven Chernausek, Lisa A Schimmenti, Benjamin Brasseur, Claudia Cesaretti, Jose E García-Ortiz, Tatiana Pineda Buitrago, Orlando Perez Silva, Jodi D Hoffman, Wolfgang Mühlbauer, Klaus W Ruprecht, Bart L Loeys, Masato Shino, Angela M Kaindl, Chie-Hee Cho, Cynthia C Morton, Richard R Meehan, Veronica van Heyningen, Eric C Liao, Ravikumar Balasubramanian, Janet E Hall, Stephanie B Seminara, Daniel Macarthur, Steven A Moore, Koh-ichiro Yoshiura, James F Gusella, Joseph A Marsh, John M Graham Jr, Angela E Lin, Nicholas Katsanis, Peter L Jones, William F Crowley Jr, Erica E Davis, David R FitzPatrick & Michael E Talkowski
In the supplementary information originally posted online, conversion errors introduced during the production of the PDF of supplementary figures corrupted some of the text in Supplementary Figure 1, the figure legend for Supplementary Figure 3 and Supplementary Figure 9. The errors have been corrected in this file as of 20 March 2017.
Supplementary Figure 9. Western blotting of SMCHD1 in arhinia cases and familial controls
Western blotting was performed on 10 arhinia cases, 11 unaffected familial controls, and 2 family members
(AH3, AHG5) with mutations in SMCHD1 and an arhinia-related phenotype (anosmia and hypoplastic nose).
To measure protein levels of SMCHD1 from lymphoblastoid cell lines (LCLs), we used two different anti-
SMHD1 antibodies (Bethyl, Abcam), which were normalized against both anti-tublin and anti-beta actin
loading controls. b) SMCHD1 protein levels were consistently lower in subjects with an SMCHD1 mutation
versus familial controls but none of the comparisons across different anti-SMCHD1 antibodies and loading
controls showed a statistically significant difference. Boxplots were created with BoxPlotR2
(http://boxplot.tyerslab.com c) We found a high correlation (r=0.77,r=0.83) between the different anti-
SMCHD1 antibodies regardless of loading control.
Nature Genetics: doi:10.1038/ng.3743
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Supplemental Figure 10. QQ Plot of differential expression analysis between arhinia cases and familial
controls.
Expression of transcription was compared between 10 arhinia cases and 10 familial controls using a two-sample
permutated test. P-values from this analysis largely match an expected distribution under the null hypothesis
(red line).
Nature Genetics: doi:10.1038/ng.3743
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Supplemental Figure 11. Repeat expression analysis in normal and affected SMCHD1 mutant subjects.
RNAseq libraries were filtered for uniquely mapped reads and counts overlapping the hg19 repeatmasker
annotation were computed. The R packages egdeR3 and DeSeq24 were implemented to perform library
normalization and differential expression. Data was filtered for individual repeat classes (LTR, L1, L2, Satellite
& SINE) and median read counts were computed per normal/affected individual. The R package beeswarm5
was used to plot the range of median read counts. Student’s t-tests were used to compare controls and patients.
Controls (green); patients (red)
References
1. Kircher, M. et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46, 310-5 (2014).
2. Spitzer, M., Wildenhain, J., Rappsilber, J. & Tyers, M. BoxPlotR: a web tool for generation of box plots. Nat Methods 11, 121-2 (2014).
3. Robinson, M.D., McCarthy, D.J. & Smyth, G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139-40 (2010).
4. Love, M.I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550 (2014).
5. Eklund, A. Beeswarm: the bee swarm plot, an alternative to stripchart. R package version 0.1. 1, 2011. (2015).
Read
cou
nts
Control
LTR
Patient
L1 L2 Satellite SINE200
0
p > 0.05 p > 0.05 p > 0.05 p > 0.05 p > 0.05
Figure x. Repeat expression analysis in normal and affected SMCHD1 mutant cases. RNAseqlibraries were filtered for uniquely mapped reads and counts overlapping the hg19 repeatmasker annotationwere computed. The R packages ‘egdeR’ and ‘DeSeq2’ were implemented to perform library normalisationand differential expression. Data was filtered for individual repeat classes (LTR, L1, L2, Satellite & SINE) and medianread counts were computed per normal/affected individual. The R package ‘beeswarm’ was used to plotthe range of median read counts. Student’s t-tests were used to compare controls and patients.