Identification of Neurofibromatosis 1 (NF1) Homologous Loci by Direct Sequencing, Fluorescence in Situ Hybridization, and PCR Amplification of Somatic Cell Hybrids

Purandare, Smita M.; Breidenbach, Heidi Huntsman; Liu, Ying; Zhu, Xiao Lin; Sawada, Shuichi; Neil, Shannon M.; Brothman, Arthur R.; White, Ray; Cawthon, Richard M.; Viskochil, David

doi:10.1006/geno.1995.1268

Cited by 38 publications

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“…4,7,11 The phylogenetic tree in Figure 3 demonstrates that the new pseudogenes are highly related to the other pseudogenes on chromosomes 2, 14, and 22. Moreover, they all contain the same exons and the transition of intron 19a to intron 27a, the latter marking the deletion of the GAP-related domain encoding exons.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11] Most of the NF1 pseudogenes have been mapped to pericentromeric regions.…”

Section: Introductionmentioning

confidence: 99%

“…On chromosomes 14 and 15, respectively two and three different NF1 pseudogene copies have been found. [3][4][5]7,10,11 In this study, we investigated the mechanism of spreading of NF1 pseudogenes, in particular those on chromosomes 2, 14, and 22. In a previous report, 9 we showed that cosmids containing the chromosome 22 NF1 pseudogene only crosshybridise with the NF1 pseudogene regions on chromosomes 2 and 14.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of spreading of the highly related neurofibromatosis type 1 (NF1) pseudogenes on chromosomes 2, 14 and 22

et al. 2000

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Neurofibromatosis type 1 (NF1) is a frequent hereditary disorder that involves tissues derived from the embryonic neural crest. Besides the functional gene on chromosome arm 17q, NF1-related sequences (pseudogenes) are present on a number of chromosomes including 2, 12, 14, 15, 18, 21, and 22. We elucidated the complete nucleotide sequence of the NF1 pseudogene on chromosome 22. Only the middle part of the functional gene but not exons 21-27a, encoding the functionally important GAP-related domain of the NF1 protein, is presented in this pseudogene. In addition to the two known NF1 pseudogenes on chromosome 14 we identified two novel variants. A phylogenetic tree was constructed, from which we concluded that the NF1 pseudogenes on chromosomes 2, 14, and 22 are closely related to each other. Clones containing one of these pseudogenes cross-hybridised with the other pseudogenes in this subset, but did not reveal any in situ hybridisation with the functional NF1 gene or with NF1 pseudogenes on other chromosomes. This suggests that their hybridisation specificity is mainly determined by homologous sequences flanking the pseudogenes. Strong support for this concept was obtained by sequence analysis of the flanking regions, which revealed more than 95% homology. We hypothesise that during evolution this subset of NF1 pseudogenes initially arose by duplication and transposition of the middle part of the functional NF1 gene to chromosome 2. Subsequently, a much larger fragment, including flanking sequences, was duplicated and gave rise to the current NF1 pseudogene copies on chromosomes 14 and 22.

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Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11] Most of the NF1 pseudogenes have been mapped to pericentromeric regions.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanism of spreading of the highly related neurofibromatosis type 1 (NF1) pseudogenes on chromosomes 2, 14 and 22

et al. 2000

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“…For sequence analysis of genomic DNA exon 7 was PCR amplified using primers as described (Purandare et al, 1995).…”

Section: Methodsmentioning

confidence: 99%

Three different premature stop codons lead to skipping of exon 7 in neurofibromatosis type I patients

et al. 2000

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Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder affecting one in 3,500 individuals. The mutation rate in the NF1 gene is one of the highest known for human genes. Compared to other methods, the protein truncation test (PTT) provides improved efficiency in detecting NF1 mutations which are dispersed throughout the gene which spans 350 kilobases of genomic DNA. We have applied the PTT and subsequent sequence analysis of cloned cDNA to identify mutations in NF1 patients. We report here the identification of two novel (W336X and Q315X), and one recurrent (R304X) mutation located in exon 7 and show that all three premature termination codons lead to skipping of exon 7 in a proportion of the transcripts derived from the mutated allele. Possible mutation-induced alterations of the RNA secondary structure and their impact on skipping of exon 7 of the NF1 gene are explored and discussed.

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“…Néanmoins, seule une petite fraction des mutations NF1 surviennent sur des sites CpG [20]. Des gènes ayant une certaine similarité de séquence avec NF1 sont pré-sents sur les chromosomes 2, 12, 14, 15, 18, 20, 21 et 22 [21,22]. La conversion génique entre un pseudogène non homologue et NF1 pourrait produire quelques mutations.…”

Section: Mutations Du Gène Nf1unclassified

La neurofibromatose 1

Wolkenstein

2001

Med Sci (Paris)

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Identification of Neurofibromatosis 1 (NF1) Homologous Loci by Direct Sequencing, Fluorescence in Situ Hybridization, and PCR Amplification of Somatic Cell Hybrids

Cited by 38 publications

References 0 publications

Mechanism of spreading of the highly related neurofibromatosis type 1 (NF1) pseudogenes on chromosomes 2, 14 and 22

Mechanism of spreading of the highly related neurofibromatosis type 1 (NF1) pseudogenes on chromosomes 2, 14 and 22

Three different premature stop codons lead to skipping of exon 7 in neurofibromatosis type I patients

La neurofibromatose 1

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