RGD Reference Report - Genetic mapping and exome sequencing identify 2 mutations associated with stroke protection in pediatric patients with sickle cell anemia. - Rat Genome Database

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Genetic mapping and exome sequencing identify 2 mutations associated with stroke protection in pediatric patients with sickle cell anemia.

Authors: Flanagan, Jonathan M  Sheehan, Vivien  Linder, Heidi  Howard, Thad A  Wang, Yong-Dong  Hoppe, Carolyn C  Aygun, Banu  Adams, Robert J  Neale, Geoffrey A  Ware, Russell E 
Citation: Flanagan JM, etal., Blood. 2013 Apr 18;121(16):3237-45. doi: 10.1182/blood-2012-10-464156. Epub 2013 Feb 19.
RGD ID: 13204735
Pubmed: PMID:23422753   (View Abstract at PubMed)
PMCID: PMC3630835   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2012-10-464156   (Journal Full-text)

Stroke is a devastating complication of sickle cell anemia (SCA), occurring in 11% of patients before age 20 years. Previous studies of sibling pairs have demonstrated a genetic component to the development of cerebrovascular disease in SCA, but few candidate genetic modifiers have been validated as having a substantial effect on stroke risk. We performed an unbiased whole-genome search for genetic modifiers of stroke risk in SCA. Genome-wide association studies were performed using genotype data from single-nucleotide polymorphism arrays, whereas a pooled DNA approach was used to perform whole-exome sequencing. In combination, 22 nonsynonymous variants were identified and represent key candidates for further in-depth study. To validate the association of these mutations with the risk for stroke, the 22 candidate variants were genotyped in an independent cohort of control patients (n = 231) and patients with stroke (n = 57) with SCA. One mutation in GOLGB1 (Y1212C) and another mutation in ENPP1 (K173Q) were confirmed as having significant associations with a decreased risk for stroke. These mutations were discovered and validated by an unbiased whole-genome approach, and future studies will focus on how these functional mutations may lead to protection from stroke in the context of SCA.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ENPP1HumanStroke susceptibilityIAGP associated with Anemia more ...RGD 
Enpp1RatStroke susceptibilityISOENPP1 (Homo sapiens)associated with Anemia more ...RGD 
Enpp1MouseStroke susceptibilityISOENPP1 (Homo sapiens)associated with Anemia more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ENPP1HumanAbnormal cerebral vascular morphology susceptibilityIAGP associated with Anemia more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Enpp1  (ectonucleotide pyrophosphatase/phosphodiesterase 1)

Genes (Mus musculus)
Enpp1  (ectonucleotide pyrophosphatase/phosphodiesterase 1)

Genes (Homo sapiens)
ENPP1  (ectonucleotide pyrophosphatase/phosphodiesterase 1)


Additional Information