Genomic profiling identifies novel mutations and SNPs in ABCD1 gene: a molecular, biochemical and clinical analysis of X-ALD cases in India
| Autor: | Veena Kalra, Satinder Aneja, Neeraj Kumar, Surendra Kumar Bansal, Madhuri Behari, Krishna K. Taneja |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Genetic Screens Gene Expression lcsh:Medicine medicine.disease_cause Biochemistry ATP Binding Cassette Transporter Subfamily D Member 1 Molecular Cell Biology Genome Sequencing Adrenoleukodystrophy Child lcsh:Science Genetics education.field_of_study Mutation Multidisciplinary Neurodegenerative Diseases Genomics Neurology Child Preschool Medicine Female Sequence Analysis Research Article Adolescent Nonsense mutation Population Blotting Western Mutation Missense India Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Frameshift mutation Cell Line Molecular Genetics Young Adult Germline mutation Genetic Mutation medicine Humans education Gene Germ-Line Mutation Clinical Genetics Evolutionary Biology Population Biology Point mutation lcsh:R Proteins Computational Biology Human Genetics X-Linked Genetics of Disease Genetic Polymorphism ATP-Binding Cassette Transporters lcsh:Q Molecular Neuroscience Population Genetics Neuroscience |
| Zdroj: | PLoS ONE, Vol 6, Iss 9, p e25094 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encode the peroxisomal membrane protein. We conducted a genomic and protein expression study of susceptibility gene with its clinical and biochemical analysis. To the best of our knowledge this is the first preliminary comprehensive study in Indian population that identified novel mutations and SNPs in a relatively large group. We screened 17 Indian indigenous X-linked adrenoleukodystrophy cases and 70 controls for mutations and SNPs in the exonic regions (including flanking regions) of ABCD1 gene by direct sequencing with ABI automated sequencer along with Western blot analysis of its endogenous protein, ALDP, levels in peripheral blood mononuclear cells. Single germ line mutation was identified in each index case in ABCD1 gene. We detected 4 novel mutations (2 missense and 2 deletion/insertion) and 3 novel single nucleotide polymorphisms. We observed a variable protein expression in different patients. These findings were further extended to biochemical and clinical observations as it occurs with great clinical expression variability. This is the first major study in this population that presents a different molecular genetic spectrum as compared to Caucasian population due to geographical distributions of ethnicity of patients. It enhances our knowledge of the causative mutations of X-ALD that grants holistic base to develop effective medicine against X-ALD. |
| Databáze: | OpenAIRE |
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