Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. II. Determination of molecular genetic origins of rearrangements

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dc.contributor.author Mohandas, N
dc.contributor.author Kan, Y W
dc.contributor.author Agre, P
dc.contributor.author Rim, K
dc.contributor.author Marchesi, J
dc.contributor.author Conboy, J
dc.date.accessioned 2010-02-03T20:16:02Z
dc.date.available 2010-02-03T20:16:02Z
dc.date.issued 1990-08
dc.identifier.citation J Clin Invest. 1990 August; 86(2): 524–530. doi: 10.1172/JCI114739 en
dc.identifier.uri http://jhir.library.jhu.edu/handle/1774.2/33793
dc.description.abstract Protein 4.1 is an approximately 80-kD structural protein in the membrane skeleton which underlies and supports the erythrocyte plasma membrane. The preceding companion paper presents a biochemical study of two abnormal protein 4.1 species from individuals with the red blood cell disorder, hereditary elliptocytosis. These variants, "protein 4.1(68/65)" and "protein 4.1(95)," have altered molecular weights due to internal deletions and duplications apparently localized around the spectrin-actin binding domain. Here we use polymerase chain reaction (PCR) techniques to clone and sequence the corresponding mutant reticulocyte mRNAs, and correlate the deletion/duplication end points with exon boundaries of the gene. Protein 4.1(68/65) mRNA lacks sequences encoding the functionally important spectrin-actin binding domain due to a 240 nucleotide (nt) deletion spanning the codons for Lys407-Gly486. Protein 4.1(95) mRNA encodes a protein with two spectrin-actin binding domains by virtue of a 369 nt duplication of codons for Lys407-Gln529. These deletions and duplications correspond to gene rearrangements involving three exons encoding 21, 59, and 43 amino acids, respectively. The duplicated 21 amino acid exon in the 4.1(95) gene retains its proper tissue-specific expression pattern, being spliced into reticulocyte 4.1 mRNA and out of lymphocyte 4.1 mRNA. en
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dc.language.iso en_US en
dc.publisher American Society for Clinical Investigation en
dc.subject Neuropeptides en
dc.subject Membrane Proteins/genetics en
dc.subject Elliptocytosis, Hereditary/genetics en
dc.subject Cytoskeletal Proteins en
dc.title Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. II. Determination of molecular genetic origins of rearrangements en
dc.type Article en

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