Correction: Exome Sequencing in an Admixed Isolated Population IndicatesNFXL1 Variants Confer a Risk for Specific Language Impairment

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model

SUMAK KAWSAY

Con el presente trabajo buscamos apoyar a todas aquellas personas que busquen tener una calidad de vida saludable, a través de la comida. En los primeros dos capítulos del presente proyecto mostraremos la idea y el modelo de negocio que representa “Sumak Kawsay”, así como la presentación del equipo que ha creado este proyecto. Mediante el transcurso del tercer capítulo se expondrá el planeamiento estratégico utilizado, el cual propondrá los lineamientos a seguir para lograr que el proyecto tenga éxito; es en este mismo capítulo en el que daremos a conocer la visión, misión y objetivos de la empresa. Posteriormente se mostrará el diseño y la metodología de investigación de mercado que se utilizo para la validación del proyecto. En el quinto capítulo, hemos planteado un plan de marketing, a través del cual explicaremos las estrategias a seguir para llegar a los potenciales clientes y se dará a conocer el desarrollo del márquetin mix. En el siguiente capítulo, explicamos de cual será nuestro plan de operaciones y como se ejecutará para hacer caminar el proyecto. El capítulo siete contempla nuestro plan de recursos humanos, organigrama y nomina. Como parte final y fundamental esta el capitulo octavo, presentamos nuestro plan financiero, a través del cual hacemos una evaluación de los flujos de caja del proyecto, la inversión que requerirá para iniciar operaciones, los indicadores de rentabilidad y su tendencia. Por último, mostraremos las conclusiones necesarias para el proyecto.With this project we seek to support all those people who are looking to have a healthy quality of life, through food. In the first two chapters of the project we will show the idea and the business model represented by "Sumak Kawsay", as well as the presentation of the team that has created this project. Through the course of the third chapter, the strategic planning used will be presented, which will propose the guidelines to follow in order to make the project successful; it is in this same chapter that we will present the vision, mission and objectives of the company. Subsequently, the design and market research methodology that was used to validate the project will be shown. In the fifth chapter, we have proposed a marketing plan, through which we will explain the strategies to be followed in order to reach potential customers and we will inform about the development of the marketing project. In the next chapter, we explain what our plan of operations will be and how it will be executed to make the project walk. Chapter Seven contemplates our human resources plan, organization chart and payroll. As final and fundamental part is the eighth chapter, we present our financial plan, through which we evaluate the cash flows of the project, the investment that will be required to start operations, the profitability indicators and their trend. Finally, we will show the necessary conclusions for the project.Trabajo de investigació

Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model

Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model

<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