Variant "HBS1L:n.135427817G>A"
Search results: 2 records
Variant information
Gene:
HBS1L 
Variant:
HBS1L:n.135427817G>A 
Genomic location:
chr6:135427817(hg19) 
HGVS:
SO Term RefSeq
HBS1L-MYB:n.135427817G>A
Alias:
HBS1L:rs9402686 
dbSNP ID:
rs9402686  
GWAS trait:
leukocyte count,mean corpuscular volume 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Altered HbF levels(1) ,Altered fetal hemoglobin (HbF) levels(1)  
Details：
  • Target disease:
    Sickle Cell Anemia (DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    P=1.23×10(-4) 
    Effect:
    Common variants for BCL11A and HBS1L-MYB were strongly associated with HbF levels.
    Alias in reference:
    HBS1L:n.135427817G>A
    Reference:
    PMID29879141
    Title:
    A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia.
    Species studied:
    Human
    Abstract:
    Genetic variants at three quantitative trait loci (QTL) for fetal haemoglobin (HbF), BCL11A, HBS1L-MYB and the β-globin gene cluster, have attracted interest as potential targets of therapeutic strategies for HbF reactivation in sickle cell anaemia (SCA). We carried out the first systematic evaluation of critical single nucleotide polymorphisms at these disease modifier loci in Nigerian patients with SCA. Common variants for BCL11A and HBS1L-MYB were strongly associated with HbF levels. At both loci, secondary association signals were detected, illustrating the mapping resolution attainable in this population. For BCL11A, the two independent sites of association were represented by rs1427407 (primary site, p = 7.0 x 10(-10)) and rs6545816 (secondary site, conditioned on rs1427407: p = 0.02) and for HBS1L-MYB by rs9402686 (HMIP-2B, p = 1.23 x 10(-4)) and rs66650371 (HMIP-2A, p = 0.002). Haplotype analysis revealed similarities in the genetic architecture of BCL11A and HBS1L-MYB in Nigerian patients. Variants at both loci also alleviated anaemia. The variant allele for the γ globin gene promoter polymorphism XmnI-HBG2 was too infrequent in our patients to be evaluated in this relatively small study. Studying the large and diverse SCA patient populations in African countries such as Nigeria will be key for a clearer understanding of how these loci work and for the discovery of new disease modifier genes.
  • Target disease:
    Sickle Cell Anemia (DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered fetal hemoglobin (HbF) levels 
    Evidence:
    P=1.9×10(-13) 
    Effect:
    Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%.
    Alias in reference:
    HBS1L:rs9402686
    Reference:
    PMID21057501
    Title:
    Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation.
    Species studied:
    Human
    Abstract:
    We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and β-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production.