title: Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population.
abstract: Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by programmed motoneuron death. The survival motor neuron 1 (SMN1) gene is an SMA-determining gene and SMN2 represents an SMA-modifying gene. Here, we applied capillary electrophoresis to quantify the SMN gene dosage in 163 normal individuals, 94 SMA patients and 138 of their parents. We further quantified exons 7 and 8 in SMN1 and SMN2. We found that the SMA patients carried the highest SMN2 copies, which was inversely correlated with disease severity among its three subtypes. Increased SMN1 was significantly associated with decreased SMN2 in the normal group. We also observed that parents of type I SMA patients had significantly fewer SMN2 copies than those of types II and III patients. The hybrid SMN genes were detected in two normal individuals and one patient and her mother. These results imply that increased SMN2 copies in SMA patient group might be derived from SMN1-to-SMN2 conversion, whereas the trend that normal individuals with higher SMN1 copies simultaneously carry fewer SMN2 copies suggested a reverse conversion, SMN2-to-SMN1. Together with the identification of hybrid SMN genes, our data provided additional evidence to support that SMN1 and SMN2 gene loci are interchangeable between population groups.
authors.affiliation: Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tai-Heng
authors.initials: TH
authors.lastname: Chen
authors.forename: Ching-Cherng
authors.initials: CC
authors.lastname: Tzeng
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Wang
authors.forename: Shou-Mei
authors.initials: SM
authors.lastname: Wu
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
mesh_terms: D044466:Asian People / Q000235:genetics; D005260:Female; D005785:Gene Conversion / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000235:genetics*; D012720:Severity of Illness Index; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology
chemical_list: C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein