Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation

被引：203
作者：
Galarneau, Genevieve [2 ]
Palmer, Cameron D. [3 ,4 ,5 ,6 ]
Sankaran, Vijay G. [1 ,7 ]
Orkin, Stuart H. [1 ,7 ,8 ]
Hirschhorn, Joel N. [3 ,4 ,5 ,6 ,9 ]
Lettre, Guillaume [2 ,10 ]
机构：
[1] Childrens Hosp Boston, Div Hematol & Oncol, Boston, MA 02115 USA
[2] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada
[3] Childrens Hosp Boston, Div Genet, Boston, MA USA
[4] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA
[5] Childrens Hosp Boston, Program Genom, Boston, MA USA
[6] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA
[7] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[8] Howard Hughes Med Inst, Boston, MA 02115 USA
[9] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA
[10] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
来源：
NATURE GENETICS | 2010年 / 42卷 / 12期
关键词：
GENOME-WIDE ASSOCIATION; EXPRESSION; HBS1L-MYB; VARIANTS; BCL11A;
D O I：
10.1038/ng.707
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
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 beta-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.
引用
收藏
页码：1049 / 1051
页数：3
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