Haemophilia B due to a de novo insertion of a human-specific Alu subfamily member within the coding region of the factor IX gene.
A de novo insertion of an Alu repeated DNA element was found within exon V of the factor IX gene in a patient with severe haemophilia B. The element interrupts the reading frame of the mature factor IX at glutamic acid 96 resulting in a stop codon within the inserted sequence. The Alu repeat is 322 bp long, and the 5' region is shortened by 38 bp. The insertion created a target site duplication of 15 bp consistent with retroposition, and contains a pure polyadenine tract of at least 78 resides at the 3' end. The nucleotide sequence agrees with a consensus for an Alu subfamily which is evolutionarily the most recently inserted, suggesting that it is an exact copy of a putative source gene. These observations indicate that retroposition of Alu elements is a continual process and a mechanism for generating human genetic defects.
Vidaud
D
D
INSERM U.91, Laboratoire de Génétique Moléculaire, Hôpital Henri-Mondor, Paris, France.
Vidaud
M
M
Bahnak
B R
BR
Siguret
V
V
Gispert Sanchez
S
S
Laurian
Y
Y
Meyer
D
D
Goossens
M
M
Lavergne
J M
JM
D001483:Base Sequence; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005164:Factor IX / Q000235:genetics*; D005796:Genes; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014960:X Chromosome
D005164:Factor IX