Test size and power using detection in subsets.

1<p>Number cases and controls reduced to 100, so sequencing exhausts cases.</p><p>For each line, except the last, 500 cases and 500 controls are generated in 5,000 simulated samples to estimate test size or power for a nominal 0.05-level test comparing the collective frequency of rare alleles. In each scenario, the baseline disease rate is 1%, so relative risk (RR) of 2.5 implies a penetrance of 2.5%. <b>Rare</b> is the number of unknown rare alleles in the population, all assumed to have the same frequency and penetrance. <b>Freq</b> is the total frequency of all rare alleles (<i>e.g.</i> 20 rare alleles with a combined frequency of 0.2 imply a frequency of 0.01 each). We make the simplifying assumption that rare alleles are mutually exclusive. <b>Seq</b> is the total number sequenced, either concentrated in cases or equally divided (balanced) among cases and controls. All four p-value columns are from Fisher's exact text. The first three count the number of cases and controls with any of the rare alleles detected among the indiduals that are sequenced. In the <b>Naive</b> and <b>Corrected</b> columns, all sequences are from controls, but the number of detected distinct rare alleles is subtracted from the case count in the ‘Corrected’ column. <b>Balanced</b> indicates that the individuals sequenced for allele detection were equally divided between cases and controls. <b>Complete</b> denotes the test based on sequencing all cases and all controls — a much larger sequencing effort. The parenthetic numbers indicate 25th and 75th percentiles of the number of rare alleles detected in the cases-only and balanced detection strategies.</p

TDT analysis of FMS candidate genes¹.

1<p>N = number of patients with the variant out of 19; TDT = transmission disequilibrium test applied to 150 probands and their parents; ns = notsignificant.</p>2<p>t = transmitted; ut = untransmitted.</p

Characteristics of FMS probands (N = 150).

1<p>Patientg001s meet principal symptoms for ACR diagnostic criteria²¹.</p

Plasma chemokine/cytokine levelsin FMS patients with C11orf40 or <i>ZNF77</i> mutations.

<p>Ctrl: unrelated healthy controls, n = 77 (female = 48 and male = 29). WT: FMS patients with wild type (non-variant) C11orf40 and <i>ZNF77</i>, n = 53 (female = 45 and male = 8). C11orf40: FMS patients with C11orf40 mutation W32X, n = 20 (female = 13 and male = 7). ZNF77: FMS patients with <i>ZNF77</i> mutation Q100X, n = 9 (female = 7 and male = 2). P values in the first row are in comparison with unrelated healthy controls; P values in the second row are in comparison with wild type (non-variant) C11orf40 and/or <i>ZNF77</i> genes.Discovery of Potential New Gene Variants and Inflammatory Cytokine Associations with Fibromyalgia Syndrome by Whole Exome Sequencing.</p

Cytokine secretion of TLR-ligand-treated monocytes transfected with wild type or mutated C11orf40 gene.

<p>Human monocytes were transfected with empty vector (V),wild type C11orf40 (WT) or the W32X truncated mutant gene (T) and challenged with three TLR ligands, LPS (TLR4), CL075 (TLR7/8), and Pam3CSK (TLR 1/2), followed by measurement of secreted cytokine 24 hrs. later. P values are for comparison to vector control (**, P = 0.005) or WT (^##, P = 0.005).</p

Summary of Colorectal Cancer Linkage Results with HLOD Scores>3.0.

a<p>Genotyped SNP nearest to the peak of the linkage region; distances are reported in bp based on the NCBI build 36.2 and Haldane cM.</p>b<p>Pseudo-gene.</p>c<p>Non-parametric Kong & Cox LOD.</p

Genome-wide Linkage Scans of White pMMR Family Groups with HLOD Score>3.0.

<p>HLOD scores from genome-wide linkage scan of five white pMMR family subgroups. The blue line represents HLODs under the dominant model and the red line represents the HLODs under the recessive model. Maximum observed HLODs>3.0 (in parenthesis) are labeled with the nearest SNP in four regions. (A) Family mean age at diagnosis <50 years (N = 58). (B) All families (N = 356). (C) Families with four or more affected members (N = 67). (D) Clinic-based families (N = 88). (E) Families with two affected members (N = 200).</p

Summary of Colorectal Cancer Linkage Results with Maximum Observed HLOD Scores between 2.0 and 3.0.

a<p>Genotyped SNP nearest to the peak of the linkage region; distances are reported based on the NCBI build 36.2 and Haldane cM.</p>b<p>SNP location and the distance in bp is given in regards to the nearest gene.</p>c<p>Ascertainment method not reported.</p>d<p>Pseudo-gene.</p

Characteristics of 356 White Colorectal Cancer Families with No Evidence of Defective Mismatch Repair, N (%).

a<p>Ascertainment method not reported.</p>b<p>Microsatellite stability of the tumor; MSS indicates that the tumor was microsatellite stable; MSI-L indicates that the tumor had low microsatellite instability; Unknown indicates that the tumor stability status was not available.</p>c<p>Mismatch repair status of the tumor by immunohistochemical analysis; No loss indicates that the tumor showed complete presence of protein expression of all the MMR genes tested (MLH1, MSH2, MSH6, and PMS2); Unknown indicates that the tumor MMR-expression status was not available.</p>d<p>Unknown for both MSI and IHC on 67 families is due to not being tested but had a LOD<0.04 within 20 kb surrounding <i>MSH2</i>, <i>MLH1</i>, <i>MSH6</i>, <i>PMS2</i>, <i>PMS1</i>, <i>MSH3</i>, or <i>MLH3</i>.</p

The overlap in the distribution of family groups.

<p>The overlap in the distribution of family groups.</p