Genetic mapping and exome sequencing identify variants associated with five novel diseases.
PLoS One
; 7(1): e28936, 2012.
Article
en En
| MEDLINE
| ID: mdl-22279524
ABSTRACT
The Clinic for Special Children (CSC) has integrated biochemical and molecular methods into a rural pediatric practice serving Old Order Amish and Mennonite (Plain) children. Among the Plain people, we have used single nucleotide polymorphism (SNP) microarrays to genetically map recessive disorders to large autozygous haplotype blocks (meanâ=â4.4 Mb) that contain many genes (meanâ=â79). For some, uninformative mapping or large gene lists preclude disease-gene identification by Sanger sequencing. Seven such conditions were selected for exome sequencing at the Broad Institute; all had been previously mapped at the CSC using low density SNP microarrays coupled with autozygosity and linkage analyses. Using between 1 and 5 patient samples per disorder, we identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. Our results reveal the power of coupling new genotyping technologies to population-specific genetic knowledge and robust clinical data.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Mapeo Cromosómico
/
Análisis de Secuencia de ADN
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Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
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Exoma
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
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Child, preschool
/
Humans
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Infant
/
Newborn
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos