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

页码：1049 / 1051

页数：3

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