Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia

Julie Makani; Stephan Menzel; Siana Nkya; Sharon E. Cox; Emma Drasar; Deogratius Soka; Albert N. Komba; Josephine Mgaya; Helen Rooks; Nisha Vasavda; Gregory Fegan; Charles R. Newton; Martin Farrall; Swee Lay Thein

doi:10.1182/blood-2010-08-302703

Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia

Julie Makani, Stephan Menzel, Siana Nkya, Sharon E. Cox, Emma Drasar, Deogratius Soka, Albert N. Komba, Josephine Mgaya, Helen Rooks, Nisha Vasavda, Gregory Fegan, Charles R. Newton, Martin Farrall, Swee Lay Thein

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Abstract

Fetal hemoglobin (HbF, alpha(2)gamma(2)) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in beta-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.

Original language	English
Pages (from-to)	1390 - 1392
Number of pages	3
Journal	Blood
Volume	117
Issue number	4
DOIs	https://doi.org/10.1182/blood-2010-08-302703
Publication status	Published - 27 Jan 2011

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@article{efc64496e30f47a0a4ab21f29980c3fa,

title = "Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia",

abstract = "Fetal hemoglobin (HbF, alpha(2)gamma(2)) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in beta-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.",

author = "Julie Makani and Stephan Menzel and Siana Nkya and Cox, {Sharon E.} and Emma Drasar and Deogratius Soka and Komba, {Albert N.} and Josephine Mgaya and Helen Rooks and Nisha Vasavda and Gregory Fegan and Newton, {Charles R.} and Martin Farrall and Thein, {Swee Lay}",

year = "2011",

month = jan,

day = "27",

doi = "10.1182/blood-2010-08-302703",

language = "English",

volume = "117",

pages = "1390 -- 1392",

journal = "Blood",

issn = "1528-0020",

publisher = "American Society of Hematology",

number = "4",

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TY - JOUR

T1 - Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia

AU - Makani, Julie

AU - Menzel, Stephan

AU - Nkya, Siana

AU - Cox, Sharon E.

AU - Drasar, Emma

AU - Soka, Deogratius

AU - Komba, Albert N.

AU - Mgaya, Josephine

AU - Rooks, Helen

AU - Vasavda, Nisha

AU - Fegan, Gregory

AU - Newton, Charles R.

AU - Farrall, Martin

AU - Thein, Swee Lay

PY - 2011/1/27

Y1 - 2011/1/27

N2 - Fetal hemoglobin (HbF, alpha(2)gamma(2)) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in beta-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.

AB - Fetal hemoglobin (HbF, alpha(2)gamma(2)) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in beta-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.

U2 - 10.1182/blood-2010-08-302703

DO - 10.1182/blood-2010-08-302703

M3 - Article

SN - 1528-0020

VL - 117

SP - 1390

EP - 1392

JO - Blood

JF - Blood

IS - 4

ER -

Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia

Abstract

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