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Genetics of low spinal muscular atrophy carrier frequency in sub‐Saharan Africa
Author(s) -
Sangaré Modibo,
Hendrickson Brant,
Sango Hammadoun Ali,
Chen Kelian,
Nofziger Jonathan,
Amara Abdelbasset,
Dutra Amalia,
Schindler Alice B.,
Guindo Aldiouma,
Traoré Mahamadou,
Harmison George,
Pak Evgenia,
Yaro Fatoumata N'Go,
Bricceno Katherine,
Grunseich Christopher,
Chen Guibin,
Boehm Manfred,
Zukosky Kristen,
Bocoum Nouhoum,
Meilleur Katherine G.,
Daou Fatoumata,
Bagayogo Koumba,
Coulibaly Yaya Ibrahim,
Diakité Mahamadou,
Fay Michael P.,
Lee HeeSuk,
Saad Ali,
Gribaa Moez,
Singleton Andrew B.,
Maiga Youssoufa,
Auh Sungyoung,
Landouré Guida,
Fairhurst Rick M.,
Burnett Barrington G.,
Scholl Thomas,
Fischbeck Kenneth H.
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24114
Subject(s) - smn1 , spinal muscular atrophy , sma* , biology , genetics , locus (genetics) , gene duplication , gene , copy number variation , allele , mathematics , combinatorics , genome
Objective Spinal muscular atrophy (SMA) is one of the most common severe hereditary diseases of infancy and early childhood in North America, Europe, and Asia. SMA is usually caused by deletions of the survival motor neuron 1 ( SMN1 ) gene. A closely related gene, SMN2 , modifies the disease severity. SMA carriers have only 1 copy of SMN1 and are relatively common (1 in 30–50) in populations of European and Asian descent. SMN copy numbers and SMA carrier frequencies have not been reliably estimated in Malians and other sub‐Saharan Africans. Methods We used a quantitative polymerase chain reaction assay to determine SMN1 and SMN2 copy numbers in 628 Malians, 120 Nigerians, and 120 Kenyans. We also explored possible mechanisms for SMN1 and SMN2 copy number differences in Malians, and investigated their effects on SMN mRNA and protein levels. Results The SMA carrier frequency in Malians is 1 in 209, lower than in Eurasians. Malians and other sub‐Saharan Africans are more likely to have ≥3 copies of SMN1 than Eurasians, and more likely to lack SMN2 than Europeans. There was no evidence of gene conversion, gene locus duplication, or natural selection from malaria resistance to account for the higher SMN1 copy numbers in Malians. High SMN1 copy numbers were not associated with increased SMN mRNA or protein levels in human cell lines. Interpretation SMA carrier frequencies are much lower in sub‐Saharan Africans than in Eurasians. This finding is important to consider in SMA genetic counseling in individuals with black African ancestry. Ann Neurol 2014;75:525–532