Spinal muscular atrophy(SMA)is caused by dysfunction of the alpha motor neurons of the spinal cord.It is an autosomal recessive disease associated to the SMN1 gene,located in the subtelomeric region of 5q13.A paralog ...Spinal muscular atrophy(SMA)is caused by dysfunction of the alpha motor neurons of the spinal cord.It is an autosomal recessive disease associated to the SMN1 gene,located in the subtelomeric region of 5q13.A paralog SMN2 gene is located at the centromeric region of the same chromosome,which apparently originated by an ancestral inverted duplication occurring only in humans.The exon sequence differs in two nucleotides in exon 7 and exon 8,which leads to an SMN2 transcript that lacks exon 7 and results in a truncated protein.Part(10%)of the SMN2 transcripts avoids the splicing of exon 7 but most of the copies are dysfunctional.In a disease scenario,the more SMN2 copies the higher possibility to restore at least partly the effects of SMN1 deficiency.Some therapeutic approaches are being developed to increase the expression of SMN2.To determine the number of SMN1 and SMN2 copies,the methodology must distinguish accurately between both genes.In this work,we present the results obtained using multiplex ligation-dependent probe amplification(MLPA)in 60 SMA suspected patients/carriers derived from different regions of Argentina.In 32 of these DNA samples we found alterations in SMN1.Among these,16 presented a heterozygous deletion(carrier status)and 14 an homozygous deletion(patient status)in exon 7 and 8 of SMN1.In one case,exon 7 was found homozygously deleted but exon 8 presented a single copy,and in another case,exon 7 was found heterozygously deleted while exon 8 was normal.Almost half of the patients(7/15)presented a normal diploid number of SMN2 while the other half(8/15)presented an increased number.In this work we showed how a probe-based methodology such as MLPA was able to distinguish between the paralog genes and determine the amount of copies in DNA samples from suspected patients/carriers of SMA.展开更多
The historical relationships of nine areas of endemism of the tropical montane cloud forests(TMCFs)were analysed based on a temporal cladistic biogeographical approach.Three cladistic biogeographical analyses were con...The historical relationships of nine areas of endemism of the tropical montane cloud forests(TMCFs)were analysed based on a temporal cladistic biogeographical approach.Three cladistic biogeographical analyses were conducted based on 29cladograms of terrestrial taxa by partitioning them into three time-slices,namely,Miocene,Pliocene,and Pleistocene.The results showed different area relationships over time.For the Miocene and Pliocene time slices,the Isthmus of Tehuantepec acted as a geographic barrier that fragmented the TMCFs into two portions:west of the Isthmus and east of the Isthmus.In the case of the Pleistocene,the TMCFs were broken into two portions,one related to the Neotropical region and the other to the Nearctic region.Furthermore,the analyses allowed us to detect the influences of different geological and paleoclimatological events on the distribution of the TMCFs over time.Therefore,the TMCFs current distribution might have been driven by geological events during the Miocene-Pliocene,whereas climatic fluctuations have the highest impact during the Pleistocene.展开更多
基金Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgements We thank Dr Jiang Zhu （Shanghai institute of hematology, Rui Jin hospital） and Dr Nelly Kieffer （CNRS LIA, Rui Jin hospital） for their comments. This work was supported by grants from the National High Tech Program of China （863, 2006AA02Z150）, the National Science Foundation of China （30525006）, the Science and Technology Commission of Shanghai Municipality （07XD14022, 06PJ14068）, ATIP program and BNP PARIBAS.
文摘Spinal muscular atrophy(SMA)is caused by dysfunction of the alpha motor neurons of the spinal cord.It is an autosomal recessive disease associated to the SMN1 gene,located in the subtelomeric region of 5q13.A paralog SMN2 gene is located at the centromeric region of the same chromosome,which apparently originated by an ancestral inverted duplication occurring only in humans.The exon sequence differs in two nucleotides in exon 7 and exon 8,which leads to an SMN2 transcript that lacks exon 7 and results in a truncated protein.Part(10%)of the SMN2 transcripts avoids the splicing of exon 7 but most of the copies are dysfunctional.In a disease scenario,the more SMN2 copies the higher possibility to restore at least partly the effects of SMN1 deficiency.Some therapeutic approaches are being developed to increase the expression of SMN2.To determine the number of SMN1 and SMN2 copies,the methodology must distinguish accurately between both genes.In this work,we present the results obtained using multiplex ligation-dependent probe amplification(MLPA)in 60 SMA suspected patients/carriers derived from different regions of Argentina.In 32 of these DNA samples we found alterations in SMN1.Among these,16 presented a heterozygous deletion(carrier status)and 14 an homozygous deletion(patient status)in exon 7 and 8 of SMN1.In one case,exon 7 was found homozygously deleted but exon 8 presented a single copy,and in another case,exon 7 was found heterozygously deleted while exon 8 was normal.Almost half of the patients(7/15)presented a normal diploid number of SMN2 while the other half(8/15)presented an increased number.In this work we showed how a probe-based methodology such as MLPA was able to distinguish between the paralog genes and determine the amount of copies in DNA samples from suspected patients/carriers of SMA.
基金the CONACyT 478077partially financed by DGAPA-PAPIIT 220621。
文摘The historical relationships of nine areas of endemism of the tropical montane cloud forests(TMCFs)were analysed based on a temporal cladistic biogeographical approach.Three cladistic biogeographical analyses were conducted based on 29cladograms of terrestrial taxa by partitioning them into three time-slices,namely,Miocene,Pliocene,and Pleistocene.The results showed different area relationships over time.For the Miocene and Pliocene time slices,the Isthmus of Tehuantepec acted as a geographic barrier that fragmented the TMCFs into two portions:west of the Isthmus and east of the Isthmus.In the case of the Pleistocene,the TMCFs were broken into two portions,one related to the Neotropical region and the other to the Nearctic region.Furthermore,the analyses allowed us to detect the influences of different geological and paleoclimatological events on the distribution of the TMCFs over time.Therefore,the TMCFs current distribution might have been driven by geological events during the Miocene-Pliocene,whereas climatic fluctuations have the highest impact during the Pleistocene.
