title: Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Institute of Biomedical Sciences, George Washington University, Washington, DC.
authors: Modibo
authors: M
authors: Sangaré
authors: Brant
authors: B
authors: Hendrickson
authors: Hammadoun Ali
authors: HA
authors: Sango
authors: Kelian
authors: K
authors: Chen
authors: Jonathan
authors: J
authors: Nofziger
authors: Abdelbasset
authors: A
authors: Amara
authors: Amalia
authors: A
authors: Dutra
authors: Alice B
authors: AB
authors: Schindler
authors: Aldiouma
authors: A
authors: Guindo
authors: Mahamadou
authors: M
authors: Traoré
authors: George
authors: G
authors: Harmison
authors: Evgenia
authors: E
authors: Pak
authors: Fatoumata N'Go
authors: FN
authors: Yaro
authors: Katherine
authors: K
authors: Bricceno
authors: Christopher
authors: C
authors: Grunseich
authors: Guibin
authors: G
authors: Chen
authors: Manfred
authors: M
authors: Boehm
authors: Kristen
authors: K
authors: Zukosky
authors: Nouhoum
authors: N
authors: Bocoum
authors: Katherine G
authors: KG
authors: Meilleur
authors: Fatoumata
authors: F
authors: Daou
authors: Koumba
authors: K
authors: Bagayogo
authors: Yaya Ibrahim
authors: YI
authors: Coulibaly
authors: Mahamadou
authors: M
authors: Diakité
authors: Michael P
authors: MP
authors: Fay
authors: Hee-Suk
authors: HS
authors: Lee
authors: Ali
authors: A
authors: Saad
authors: Moez
authors: M
authors: Gribaa
authors: Andrew B
authors: AB
authors: Singleton
authors: Youssoufa
authors: Y
authors: Maiga
authors: Sungyoung
authors: S
authors: Auh
authors: Guida
authors: G
authors: Landouré
authors: Rick M
authors: RM
authors: Fairhurst
authors: Barrington G
authors: BG
authors: Burnett
authors: Thomas
authors: T
authors: Scholl
authors: Kenneth H
authors: KH
authors: Fischbeck
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000453:epidemiology* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein