Source:http://linkedlifedata.com/resource/pubmed/id/18704959
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2008-10-1
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| pubmed:abstractText |
Mutations of ankyrin-1 are the most frequent cause of the inherited hemolytic anemia, hereditary spherocytosis (HS), in people of European ancestry. Ankyrin-1, which provides the primary linkage between the erythrocyte membrane skeleton and the plasma membrane, has numerous isoforms generated by alternative splicing, alternate polyadenylation, use of tissue-specific promoters, and alternate NH(2) or COOH-termini. Mutation detection in erythrocyte membrane protein genes, including ankyrin, has been a challenge, primarily due to the large size of these genes, and the apparent frequent occurrence of HS-associated null alleles. Using denaturing high-performance liquid chromatography (DHPLC), we screened the ankyrin gene of the proband of a large, three generation African-American kindred with ankyrin-deficient HS. DHPLC yielded an abnormal chromatogram for exon 1. Examination of the corresponding exon 1 sequence in genomic DNA from the proband revealed heterozygosity for a mutation of the initiator methionine (ATG to ATA Met 1 Ile). Coupled in vitrotranscription/translation studies with rabbit reticulocyte lysates demonstrated that the wild-type ankyrin erythroid cDNA initiates only from the known initiator methionine, indicating that the use of alternate initiator methionine is not a mechanism of isoform diversity in erythroid cells. The mutant ankyrin allele, unlike some initiator methionine mutations that utilize downstream codons for translation initiation, was associated with a null allele. This is the first report describing ankyrin-linked HS in an African-American kindred.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1096-8652
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2008 Wiley-Liss, Inc.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
83
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
789-94
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:18704959-African Americans,
pubmed-meshheading:18704959-Alleles,
pubmed-meshheading:18704959-Ankyrins,
pubmed-meshheading:18704959-Base Sequence,
pubmed-meshheading:18704959-Case-Control Studies,
pubmed-meshheading:18704959-Chromatography, High Pressure Liquid,
pubmed-meshheading:18704959-Codon,
pubmed-meshheading:18704959-DNA Mutational Analysis,
pubmed-meshheading:18704959-Exons,
pubmed-meshheading:18704959-Family,
pubmed-meshheading:18704959-Female,
pubmed-meshheading:18704959-Gene Frequency,
pubmed-meshheading:18704959-Genetic Testing,
pubmed-meshheading:18704959-Heterozygote,
pubmed-meshheading:18704959-Humans,
pubmed-meshheading:18704959-Male,
pubmed-meshheading:18704959-Molecular Sequence Data,
pubmed-meshheading:18704959-Mutation,
pubmed-meshheading:18704959-Pedigree,
pubmed-meshheading:18704959-Siblings,
pubmed-meshheading:18704959-Spherocytosis, Hereditary
|
| pubmed:year |
2008
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| pubmed:articleTitle |
Ankyrin-linked hereditary spherocytosis in an African-American kindred.
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| pubmed:affiliation |
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|