Evidence of a segregation ratio distortion of SMN1 alleles in spinal muscular atrophy

Alías, Laura; Barceló, Montserrat; Gich, Ignasi; Estapé, Marta; Parra, Johanna; Amenedo, Maria; Baiget, Montserrat; Tizzano, Eduardo F.

doi:10.1038/sj.ejhg.5201886

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…Homozygous biallelic loss was found in only 20.7% of fetuses, as opposed to the expected 25%. A similar analysis by Alias et al [31] showed statistically significant deviation in favor of the wild-type SMN1 allele. In our material, the proportion of fetuses predicted for SMA is even lower -at 18% (9/50) [32] .…”

Section: Discussionsupporting

confidence: 60%

Incidence of Spinal Muscular Atrophy in Poland – More Frequent than Predicted?

Jędrzejowska¹,

Milewski²,

Zimowski³

et al. 2010

Neuroepidemiology

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Background: The application of molecular methods has enhanced and enlarged the diagnostics of spinal muscular atrophy (SMA) and its carriership. It allows for reliable epidemiological studies which are of importance to demography and genetic counseling. Methods: This study sought to evaluate the incidence of SMA in Poland, on the basis of the prevalence of the SMN1 gene deletion carrier state in the general population, as well as an analysis of all cases of SMA diagnosed in the years 1998–2005. Results: The prevalence of the SMN1 gene deletion carrier state was estimated at 1 per 35 persons (17/600), yielding an incidence of SMA equal to 1 per 4,900. By contrast, the incidence of SMA based on the results of the meta-analysis was an estimated 1 per 7,127 in Warsaw and 1 per 9,320 persons across Poland, suggesting that some cases of SMA remain undiagnosed. SMA1 predominated among the diagnoses, accounting for 69% of all cases. Conclusion: A high prevalence of the SMN1 deletion carrier state in the general population indicates that SMA could be a more frequent disease than is predicted by the epidemiological data regarding diagnosed cases.

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Section: Discussionsupporting

confidence: 60%

Incidence of Spinal Muscular Atrophy in Poland – More Frequent than Predicted?

Jędrzejowska¹,

Milewski²,

Zimowski³

et al. 2010

Neuroepidemiology

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“…2008). Alias et al. (2007) also reported a significant segregation distortion of spinal muscular atrophy alleles, which leads to a reduced number of affected and carrier individuals.…”

Section: Resultsmentioning

confidence: 99%

“…(2007) also reported a significant segregation distortion of spinal muscular atrophy alleles, which leads to a reduced number of affected and carrier individuals. Moreover, the authors propose that meiotic drive, survival of gametes or preferential fertilization is a possible explanation for the observed biased segregation of alleles (Alias et al. 2007).…”

Section: Resultsmentioning

confidence: 99%

Analysis of segregation distortion and association of the bovine FGF2 with fertilization rate and early embryonic survival

et al. 2009

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Fibroblast growth factor 2 (FGF2) plays an important role in fertility and early embryo development. The objectives of this study were to test the association of FGF2 polymorphisms with fertilization success in cattle using an in vitro fertilization experimental system and to investigate the mechanisms leading to the presence of rare alleles of FGF2 in the Holstein population. A total of 7502 fertilizations were performed and a total of 5049 embryos were produced to collect fertilization and embryo survival records. A total of 444 ovaries, from which oocytes were aspirated and fertilized, were genotyped for two single nucleotide polymorphisms (SNPs) previously identified in FGF2 (g.23G>T and g.11646A>G). Frequency of the TT genotype of the g.23G>T SNP was low in the ovary population (5.4%) and in a different Holstein cattle population (6.6%) examined in this study. Single SNP analysis showed that both SNPs were associated with early embryonic survival rate. Two-way interaction analysis revealed significant association of epistatic interaction between the SNPs with fertilization rate. To test whether or not low frequency of allele T for the g.23G>T SNP in the population is a result of a fertilization failure of T oocytes, semen from six GG bulls was used to fertilize a total of 458 oocytes obtained from 19 GT ovaries. A significant segregation distortion was observed for 169 embryos genotyped for the g.23G>T SNP. We conclude that oocytes carrying the T allele show a reduced fertilization rate and that segregation distortion leads to rarity of the TT genotype in the population.

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Genetisches Modell der autosomal-rezessiv erblichen proximalen spinalen Muskelatrophie

Langer

Rudnik‐Schöneborn

Zerres

et al. 2013

Medizinische Genetik

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Zusammenfassung Die proximale infantile und juvenile spinale Muskelatrophie (SMA) ist eine der häufigsten autosomal-rezessive Erbkrankheiten. Man unterteilt die Patienten in 3 Gruppen, SMA Typ I-III, abhängig von der Schwere der Erkrankung (den erreichten Meilensteinen). Das hauptsächlich verantwortliche Gen, das Survival-motor-neuron(SMN1)-Gen, ist auf Chromosom 5 lokalisiert. Während das Normalallel meist mit einer oder 2 SMN1-Kopien vorliegt, sind die Defektallele bei den meisten Patienten von einer Deletion betroffen; bei einigen liegen Punktmutationen vor. Bei den Deletionen wiederum unterscheidet man zwischen einfacher und großer Deletion, die über das SMN1-Gen hinausgeht. Ein homozygotes Auftreten letzterer führt zu pränataler Letalität. Für die vorliegende Arbeit wurden zahlreiche in der Literatur verfügbare Daten zur SMA Typ I-III zusammengetragen und in ihrer Abhängigkeit in einem genetischen Modell zusammengefasst. So war es möglich, fehlende Parameter zu schätzen, um genauere Aussagen über Genotypen machen zu können. Die einzelnen Allelfrequenzen konnten wie folgt geschätzt werden: Normalallel b (1 SMN1-Kopie): ≈ 0,9527; Normalallel c (2 SMN1-Kopien): ≈ 0,0362; einfache Deletion a (0 SMN1-Kopien): ≈ 0,0104; Punktmutation d (1 SMN1-Kopie): ≈ 0,0003; große Deletion g (0 SMN1-Kopien): ≈ 0,0004. Die Genhäufigkeit beträgt etwa 1:90 mit einer Heterozygtenfrequenz von 1:46.

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Evidence of a segregation ratio distortion of SMN1 alleles in spinal muscular atrophy

Cited by 7 publications

References 12 publications

Incidence of Spinal Muscular Atrophy in Poland – More Frequent than Predicted?

Incidence of Spinal Muscular Atrophy in Poland – More Frequent than Predicted?

Analysis of segregation distortion and association of the bovine FGF2 with fertilization rate and early embryonic survival

Genetisches Modell der autosomal-rezessiv erblichen proximalen spinalen Muskelatrophie

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