Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion.
Human fibrinogen cDNA probes for the alpha-, beta-, and gamma-polypeptide chains have been used to isolate the corresponding genes from human genomic libraries. There is a single copy of each gene. Restriction endonuclease analysis of isolated genomic clones and human genomic DNA indicates that the human alpha-, beta-, and gamma-fibrinogen genes are closely linked in a 50-kilobase region of a single human chromosome: the alpha-gene in the middle flanked by the beta-gene on one side and the gamma-gene on the other. The alpha- and gamma-chain genes are oriented in tandem and transcribed toward the beta-chain gene. The beta-chain gene is transcribed from the opposite DNA strand toward the gamma- and alpha-chain genes. The three genes have been localized to the distal third of the long arm of chromosome 4, bands q23-q32, by in situ hybridization with fibrinogen cDNAs and by examination of DNA from multiple rodent-human somatic cell hybrids. Alternative explanations for the present arrangement of the three fibrinogen genes involve either a three-step mechanism with inversion of the alpha/gamma-region or a two-step mechanism involving remote transposition and inversion. The second more simple mechanism has a precedent in the origin of repeated regions of the fibrinogen and immunoglobulin genes.
Kant
J A
JA
Fornace
A J
AJ
Saxe
D
D
Simon
M I
MI
McBride
O W
OW
Crabtree
G R
GR
D005075:Biological Evolution; D002905:Chromosomes, Human, 4-5; D004251:DNA Transposable Elements; D005340:Fibrinogen / Q000235:genetics*; D005784:Gene Amplification; D008040:Genetic Linkage; D006801:Humans; D008957:Models, Genetic; D014158:Transcription, Genetic
D004251:DNA Transposable Elements; D005340:Fibrinogen