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An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene
A 130 base pair (bp) insertion (g.-8delCins130) into the 5' untranslated region of the PAFAH1B1 (LIS1) gene, seven nucleotides upstream of the translational initiation site, was detected in an isolated case of lissencephaly. The inserted DNA sequence exhibited perfect homology to two non-contig...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525223/ https://www.ncbi.nlm.nih.gov/pubmed/20846927 http://dx.doi.org/10.1186/1479-7364-4-6-384 |
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author | Millar, David S Tysoe, Carolyn Lazarou, Lazarus P Pilz, Daniela T Mohammed, Shehla Anderson, Katharine Chuzhanova, Nadia Cooper, David N Butler, Rachel |
author_facet | Millar, David S Tysoe, Carolyn Lazarou, Lazarus P Pilz, Daniela T Mohammed, Shehla Anderson, Katharine Chuzhanova, Nadia Cooper, David N Butler, Rachel |
author_sort | Millar, David S |
collection | PubMed |
description | A 130 base pair (bp) insertion (g.-8delCins130) into the 5' untranslated region of the PAFAH1B1 (LIS1) gene, seven nucleotides upstream of the translational initiation site, was detected in an isolated case of lissencephaly. The inserted DNA sequence exhibited perfect homology to two non-contiguous regions of the mitochondrial genome (8479 to 8545 and 8775 to 8835, containing portions of two genes, ATP8 and ATP6), as well as near-perfect homology (1 bp mismatch) to a nuclear mitochondrial pseudogene (NUMT) sequence located on chromosome 1p36. This lesion was not evident on polymerase chain reaction (PCR) sequence analysis of either parent, indicating that the mutation had occurred de novo in the patient. Experiments designed to distinguish between a mitochondrial and a nuclear genomic origin for the inserted DNA sequence were, however, inconclusive. Mitochondrial genome sequences from both the patient and his parents were sequenced and found to be identical to the sequence inserted into the PAFAH1B1 gene. Analysis of parental PCR products from the chromosome 1-specific NUMT were also consistent with the interpretation that the inserted sequence had originated directly from the mitochondrial genome. The chromosome 1-specific NUMT in the patient proved to be refractory to PCR analysis, however, suggesting that this region of chromosome 1 could have been deleted or rearranged. Although it remains by far the most likely scenario, in the absence of DNA sequence information from the patient's own chromosome 1-specific NUMT, we cannot unequivocally confirm that the 130 bp insertion originated from mitochondrial genome rather than from the NUMT. |
format | Online Article Text |
id | pubmed-3525223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35252232012-12-19 An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene Millar, David S Tysoe, Carolyn Lazarou, Lazarus P Pilz, Daniela T Mohammed, Shehla Anderson, Katharine Chuzhanova, Nadia Cooper, David N Butler, Rachel Hum Genomics Primary Research A 130 base pair (bp) insertion (g.-8delCins130) into the 5' untranslated region of the PAFAH1B1 (LIS1) gene, seven nucleotides upstream of the translational initiation site, was detected in an isolated case of lissencephaly. The inserted DNA sequence exhibited perfect homology to two non-contiguous regions of the mitochondrial genome (8479 to 8545 and 8775 to 8835, containing portions of two genes, ATP8 and ATP6), as well as near-perfect homology (1 bp mismatch) to a nuclear mitochondrial pseudogene (NUMT) sequence located on chromosome 1p36. This lesion was not evident on polymerase chain reaction (PCR) sequence analysis of either parent, indicating that the mutation had occurred de novo in the patient. Experiments designed to distinguish between a mitochondrial and a nuclear genomic origin for the inserted DNA sequence were, however, inconclusive. Mitochondrial genome sequences from both the patient and his parents were sequenced and found to be identical to the sequence inserted into the PAFAH1B1 gene. Analysis of parental PCR products from the chromosome 1-specific NUMT were also consistent with the interpretation that the inserted sequence had originated directly from the mitochondrial genome. The chromosome 1-specific NUMT in the patient proved to be refractory to PCR analysis, however, suggesting that this region of chromosome 1 could have been deleted or rearranged. Although it remains by far the most likely scenario, in the absence of DNA sequence information from the patient's own chromosome 1-specific NUMT, we cannot unequivocally confirm that the 130 bp insertion originated from mitochondrial genome rather than from the NUMT. BioMed Central 2010-08-01 /pmc/articles/PMC3525223/ /pubmed/20846927 http://dx.doi.org/10.1186/1479-7364-4-6-384 Text en Copyright ©2010 Henry Stewart Publications |
spellingShingle | Primary Research Millar, David S Tysoe, Carolyn Lazarou, Lazarus P Pilz, Daniela T Mohammed, Shehla Anderson, Katharine Chuzhanova, Nadia Cooper, David N Butler, Rachel An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene |
title | An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene |
title_full | An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene |
title_fullStr | An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene |
title_full_unstemmed | An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene |
title_short | An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene |
title_sort | isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived dna sequence into the 5' untranslated region of the pafah1b1 (lis1) gene |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525223/ https://www.ncbi.nlm.nih.gov/pubmed/20846927 http://dx.doi.org/10.1186/1479-7364-4-6-384 |
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