Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 1990 Feb;87(4):1551-5.

Clusters of intragenic Alu repeats predispose the human C1 inhibitor locus to deleterious rearrangements.

Author information

1
Unité d'Immunogénétique, Institut Pasteur, Paris, France.

Abstract

Frequent alterations in the structure of the complement component C1 inhibitor gene have been found in patients affected by the common variant of hereditary angioedema, characterized by low plasma levels of C1 inhibitor. This control protein limits the enzymic activity of the first component of complement and of other plasma serine proteases. Sequence comparisons of a 4.6-kilobase-long segment of the normal gene and the corresponding gene segments isolated from two patients carrying family-specific DNA deletions point to unusually long clusters of tandem repeats of the Alu sequence family as a source of genetic instability in this locus. Unequal crossovers, in a variety of registers, among Alu sequences of the clusters result in deletions of variable length that encompass exon 4. In a third family, exon 4 was instead found to be duplicated along with the same tracts of flanking introns lost in one of the deletions. In addition to undergoing Alu-mediated partial deletions and duplications, the gene is also a target for more recent retroposition events. Gross alterations in the C1 inhibitor gene account for about 20% of the hereditary angioedema chromosomes and consequently make this gene a prime example of the mutagenic liability of Alu repeats.

PMID:
2154751
PMCID:
PMC53513
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center