Polymorphisms in the myosin light chain kinase gene that confer risk of severe sepsis are associated with a lower risk of asthma  Li Gao, MD, PhD, Audrey V. Grant, MS, Nicholas Rafaels, MS, Maria Stockton-Porter, MA, Tonya Watkins, BS, Peisong Gao, MD, PhD, Peter Chi, MS, Melba Muñoz, MD, Harold Watson, MD, Georgia Dunston, PhD, Alkis Togias, MD, Nadia Hansel, MD, Jonathan Sevransky, MD, James P. Maloney, MD, Marc Moss, MD, Carl Shanholtz, MD, Roy Brower, MD, Joe G.N. Garcia, MD, Dmitry N. Grigoryev, PhD, Christopher Cheadle, PhD, Terri H. Beaty, PhD, Rasika A. Mathias, ScD, Kathleen C. Barnes, PhD  Journal of Allergy and Clinical Immunology  Volume 119, Issue 5, Pages 1111-1118 (May 2007) DOI: 10.1016/j.jaci.2007.03.019 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Genomic organization of MYLK and position of 19 tag SNPs (A) and the 3 major haplotype regions associated with asthma and total serum IgE concentrations in 2 independent, family-based populations of African descent (B). Exons are represented by blue boxes. Positions and MAF of 19 tag SNPs are represented by vertical lines below the gene structure (pink, African Caribbean; green, African American). C, Protein domain structure of MYLK in relation to the 3 haplotype blocks displayed in B. The immunoglobulin (IG) cell adhesion molecule subfamily (IGcam) domains are displayed as rectangular boxes in blue; the fibronectin type III (FN3) domain is displayed as a circle in green, and the serine/threonine protein kinase (S_TKc) domain is represented by rectangular boxes in red. smMYLK shares the identical FN3, S_TKc, and 3 of the immunoglobulin/IGcam domains with nmMYLK. Journal of Allergy and Clinical Immunology 2007 119, 1111-1118DOI: (10.1016/j.jaci.2007.03.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 FBAT results showing global −log10 (P value) against chromosomal location for (A) asthma and (B) log[total IgE] concentrations in African Caribbean families. Two-point and haplotype results for 2-marker, 3-marker, and 4-marker windows across the MYLK gene are illustrated. The y axis indicates the value of −log10 (P), and the x axis indicates the relative position for each SNP marker (n = 19) locus in MYLK, 5′ to 3′ direction. The black vertical line represents the position of each SNP marker on the x axis, and height of the line on the y axis indicates the value of −log10 (P). The horizontal lines in green represent the 2-SNP windowing; red represents 3-SNP windowing; and blue represents the 4-SNP windowing. Journal of Allergy and Clinical Immunology 2007 119, 1111-1118DOI: (10.1016/j.jaci.2007.03.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Summary distributions of −log10 (P value) for single MYLK SNP or haplotypes from windowing of 2-SNP to 4-SNPs across the MYLK gene in the African Caribbean and African American families. Blue circles depict the single marker (solid) and haplotype analysis (outline) results (global P values) for the African Caribbean families; a red diamond was used for the haplotype analyses in the African American families. Symbols are placed according to the last SNP from the significant haplotype windows. Journal of Allergy and Clinical Immunology 2007 119, 1111-1118DOI: (10.1016/j.jaci.2007.03.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Association between marker rs936170 (G>C) and MYLK mRNA expression. MYLK mRNA expression was detected by Illumina's Sentrix HumanRef-8 Expression BeadChips. Pairwise comparisons of MYLK expression levels between groups stratified by asthma status and genotypes at marker rs936170 were performed using the unpaired t test. Significantly decreased MYLK expression was observed in C-allele carriers with asthma (n = 9) compared with controls homozygous for the common G allele (n = 6; P = .025). No difference in MYLK expression was observed between GC subjects with asthma and either patients with asthma with GG (n = 7; P = .074) or controls with GC genotype (n = 6). The bottom, median, and top lines of the box mark the 25th, 50th and 75th percentiles, respectively. The vertical line shows the range of values between the 5th and 95th percentiles. Journal of Allergy and Clinical Immunology 2007 119, 1111-1118DOI: (10.1016/j.jaci.2007.03.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions