Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population

Chen, Tai‐Heng; Tzeng, Ching‐Cherng; Wang, Chun-Chi; Wu, Shou‐Mei; Chang, Jan-Gowth; Yang, San‐Nan; Hung, Chih‐Hsing; Jong, Yuh‐Jyh

doi:10.1016/j.jns.2011.06.002

Cited by 26 publications

(18 citation statements)

References 26 publications

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“…Reduction in copy number of SMN1 can be caused by either gene conversion or deletion [7]. There was bidirectional gene conversion between SMN1 and SMN2 in different population groups [8]. As early as 1997, the physical evidence was presented for conversion of SMN1-to-SMN2 in SMA patients and carriers [9,10].…”

Section: Discussionmentioning

confidence: 99%

Transmission characteristics of SMN from 227 spinal muscular atrophy core families in China

Cao

Bai

et al. 2020

J Hum Genet

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To define the relationship between the survival motor neuron 1 gene (SMN1) and SMN2, and explore the variability of these two genes within the generations, SMN1 and SMN2 copy numbers were determined for 227 SMA families. The association analysis indicated that there was a negative correlation between the copy number of SMN1 and SMN2 (Spearman = −0.472, P < 0.001) in 227 SMA children and 454 of their parents. The average SMN copies from father and mother in each SMA family were used to represent the copy number in the parent's generation. Subsequently, SMN transmission analysis showed that the similar distribution trend of SMN1 and SMN2 copy number was not only in the SMA children and their parents' generation but also in the non-SMA families. Moreover, when the SMN2 copy number was one in the parent's generation, 75% of their SMA children had type I and 25% of them had type II/III. However, when the SMN2 copies were three in the parent's generation, all of their SMA children were type II/III. Therefore, the diversity of SMN copies was mostly inherited and the SMN2 copy number in the parent's generation could predict the disease severity of SMA children to some extent.

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Section: Discussionmentioning

confidence: 99%

Transmission characteristics of SMN from 227 spinal muscular atrophy core families in China

Cao

Bai

et al. 2020

J Hum Genet

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“…Chen et al reported that a distribution for SMN2 copy numbers in 94 Chinese SMA patients of 5 copies in 1 patient (1.1%), 4 copies in 24 (25.5%), 3 copies in 47 (50%) and 2 copies in 22 (23.4%). No patients with 0 or 1 copy of SMN2 were found in their population [ 16 ]. In addition, Qu et al reported that a distribution for SMN2 copy numbers in 232 Chinese SMA patients of 4 SMN2 copies in 13 patients (5.6%), 3 copies in 153(65.9%), 2 copies in 66(28.5%) and no patients having only 0 or 1 copy of SMN2 [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls

Fang

Zeng

et al. 2015

BMC Musculoskelet Disord

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BackgroundSpinal muscular atrophy (SMA) is caused by SMN1 dysfunction, and the copy number of SMN2 and NAIP can modify the phenotype of SMA. The aim of this study was to analyze the copy numbers and gene structures of SMA-related genes in Chinese SMA patients and unrelated healthy controls.MethodsForty-two Chinese SMA patients and two hundred and twelve unrelated healthy Chinese individuals were enrolled in our study. The copy numbers and gene structures of SMA-related genes were measured by MLPA assay.ResultsWe identified a homozygous deletion of SMN1 in exons 7 and 8 in 37 of 42 patients (88.1%); the other 5 SMA patients (11.9%) had a single copy of SMN1 exon 8. The proportions of the 212 unrelated healthy controls with different copy numbers for the normal SMN1 gene were 1 copy in 4 individuals (1.9%), 2 copies in 203 (95.7%) and 3 copies in 5 (2.4%). Three hybrid SMN genes and five genes that lack partial sequences were found in SMA patients and healthy controls. Distributions of copy numbers for normal SMN2 and NAIP were significantly different (P < 0.001) in people with and without SMA.ConclusionThe copy numbers and gene structures of SMA-related genes were different in Chinese SMA patients and healthy controls.

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“…This study assessed a total of 16 patients with different types of SMA from Kaohsiung Medical University Hospital (KMUH‐IRB‐980125). Clinical information about the patients with different types of SMA was obtained as described previously [26].…”

Section: Methodsmentioning

confidence: 99%

Survival of motor neuron protein downregulates miR‐9 expression in patients with spinal muscular atrophy

Wang

Chiou

Liao

et al. 2014

The Kaohsiung J of Med Scie

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Spinal muscular atrophy (SMA) is a lethal hereditary disease caused by homozygous absence of the survival of the motor neuron (SMN) 1 gene (SMN1), and it is the leading genetic cause of infant mortality. The severity of SMA is directly correlated with SMN protein levels in affected patients; however, the cellular regulatory mechanisms for SMN protein expression are not completely understood. In this study, we investigated the regulatory effects between SMN expression and miR-9a, a downstream noncoding small RNA. Using an inducible SMN short hairpin RNA interference (shRNAi) system in NSC 34 and human skin fibroblast cells, cellular miR-9 levels and SMN protein repression were time-dependently upregulated. Conversely, cellular miR-9 levels decreased when HeLa cells were transfected with SMN protein fused with green fluorescent protein. In SMA-like mice spinal cords and human primary skin fibroblasts isolated from patients with different degrees of SMA, human SMN exhibited a disease severity-dependent decrease, whereas cellular miR-9 levels increased. These results clearly suggested that cellular SMN proteins regulated miR-9 expression and that miR-9 expression was related to SMA severity. Thus, miR-9 may be a marker for SMA prognosis.

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Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population

Cited by 26 publications

References 26 publications

Transmission characteristics of SMN from 227 spinal muscular atrophy core families in China

Transmission characteristics of SMN from 227 spinal muscular atrophy core families in China

Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls

Survival of motor neuron protein downregulates miR‐9 expression in patients with spinal muscular atrophy

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