Recurrent DNA inversion rearrangements in the human genome.
Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome. In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located on chromosomes 3, 15, and 19, were analyzed. The relative proportion of wild-type to rearranged structures was determined in DNA samples from blood obtained from different, unrelated individuals. The results obtained indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells. Interestingly, the rearrangements studied were significantly more abundant in adults than in newborn individuals, suggesting that such DNA rearrangements might start to appear during embryogenesis or fetal life and continue to accumulate after birth. The relevance of our results in regard to human genomic variation is discussed.
Flores
Margarita
M
Centro de Ciencias Genómicas, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62210, Mexico.
Morales
Lucía
L
Gonzaga-Jauregui
Claudia
C
Domínguez-Vidaña
Rocío
R
Zepeda
Cinthya
C
Yañez
Omar
O
Gutiérrez
María
M
Lemus
Tzitziki
T
Valle
David
D
Avila
Ma Carmen
MC
Blanco
Daniel
D
Medina-Ruiz
Sofía
S
Meza
Karla
K
Ayala
Erandi
E
García
Delfino
D
Bustos
Patricia
P
González
Víctor
V
Girard
Lourdes
L
Tusie-Luna
Teresa
T
Dávila
Guillermo
G
Palacios
Rafael
R
D000328:Adult; D000367:Age Factors; D007446:Chromosome Inversion / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics*; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods; D015321:Gene Rearrangement / Q000235:genetics*; D040481:Genome Components / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D016133:Polymerase Chain Reaction / Q000379:methods; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA