Additional file 1: of An investigation of NFXL1, a gene implicated in a study of specific language impairment

Amplification of a fragment of NFXL1 cDNA in examined brain regions. Gel electrophoresis picture showing a fragment of NFXL1 cDNA amplified by regular PCR, and the PCR protocol. (PDF 46.2 kb

Additional file 7:Â Table S6. of VarElect: the phenotype-based variation prioritizer of the GeneCards Suite

Vcf file produced from the exome sequencing of the Arthrogryposis Multiplex Congenita clinical case described in the results section. (GZ 1665 kb

Additional file 2: Table S1. of VarElect: the phenotype-based variation prioritizer of the GeneCards Suite

Gene lists and corresponding phenotypes for Phenolyzer. (XLSX 32.0 kb

Additional file 6:Â Table S5. of VarElect: the phenotype-based variation prioritizer of the GeneCards Suite

Three vcf files produced from the exome sequencing of a trio belonging to the Apnea, Leigh-Like clinical case described in the results section. (GZ 13334 kb

Additional file 1: Figure S1. of VarElect: the phenotype-based variation prioritizer of the GeneCards Suite

Merging direct and indirect modes. For each tested interlacing factor (x-axis) the red line represents the count of phenotype searches (out of ~300 relevant searches) for which the highest ranking result was direct (left y-axis). The blue line represents the average “interlacing score” (right y-axis) of all relevant phenotype searches. (PDF 52 kb

Additional file 4:Â Table S3. of VarElect: the phenotype-based variation prioritizer of the GeneCards Suite

Vcf file produced from the exome sequencing of the Congenital Diarrhea clinical case described in the results section. (GZ 14654 kb

Additional file 3: Table S2. of VarElect: the phenotype-based variation prioritizer of the GeneCards Suite

Gene lists and corresponding phenotypes for Phenomyzer and Exomiser benchmarking. (XLSX 16.0 kb

<i>NFXL1</i> coding variants observed in 117 UK (SLIC) probands affected by SLI.

<p>1 – Variant allele freq (VAF) in 117 UK SLIC probands is estimated by Syzygy using the proportion of reads that have the variant</p><p>2 – Median read depth for given base across all pools</p><p>3 - Variant allele frequency (VAF) in 1000 genomes super-populations (Integrated phase I data, accessed March 2014). ALL – all 1000 genomes populations combined (No. alleles ∼ 2184), AFR – African populations (YRI, LWK, GWD, MSL, ESN, ASW & ACB, No. chromosomes = 492), AMR – Ad mixed Americans (MXL, PUR, CLM, PEL, No. chromosomes = 362),ASN – East Asian (CHB, JPT, CHS, CDX & KHV, No. chromosomes = 572), EUR-European (TSI, FIN, GBR, IBS, no. chromosomes = 758).</p><p>4 – Exome Sequencing Project (ESP) variant allele frequency (VAF). EA – European Americans (no. chromosomes = 8600), AA – African Americans (no. chromosomes = 4268).</p><p>5 – Combined variant allele frequency across European controls from 1000 genomes and EVS (no. chromosomes = 9358)</p><p>6 – Allele frequency in SLI probands after confirmatory Sanger sequencing (no. chromosomes = 234)</p><p>7 – Amino acid change conferred by given sequence variant in protein NP_694540.3. If the change occurs within a conserved motif, this is noted.</p><p>8 – Fisher’s exact test for differences in allele frequencies between EVS European Americans and SLIC probands. ns = non-significant P<0.05</p><p>NT = not tested</p><p>Ns = not significant</p><p><i>NFXL1</i> coding variants observed in 117 UK (SLIC) probands affected by SLI.</p

Putative contributory coding variants identified in <i>NFXL1</i> by this study.

<p>Position of putative <i>NFXL1</i> coding variants with respect to exons and protein coding sequence. Genomic coding exons (exons 2–23) are shown by pink bands at the top. Protein motifs are represented by colored bands in the lower boxes. The red box represents a Znf RING motif, the yellow boxes represent Znf NFX1 motifs, the blue box represents a coiled-coil domain and the green box a transmembrane domain. Putative contributory coding variants are shown by arrows. Blue arrows denote synonymous changes, red arrows nonsynonymous changes. Sanger sequencing plots are given for all variants identified. Conservation of amino acid sequences across 11 species shown for all variants identified. The ref row shows the human reference allele and the variant row shows the observed variant in our samples. All sequences that differ from the reference sequence are shown in red. </p

Coding variants observed in SLIC probands and their families.

<p>Pedigrees are shown for nuclear families of SLIC individuals carrying three coding variations in <i>NFXL1</i>. Individuals carrying the variants are identified with a black circle. Sequencing traces of each variant is shown. SLIC probands are colored in red and other family members with SLI (defined as expressive and/or receptive language skills >1.5SD below that expected for their age) are colored in orange. In pedigree 3 (rs151113647), the youngest sibling (colored in yellow) did not meet the criteria for SLI but had expressive and receptive language scores ∼1SD below that expected for his age. Individuals with no shading have typical language ability. DNA was not available for individuals colored in grey.</p