Sequence analysis of the breakpoint regions of an X;5 translocation in a female with Duchenne muscular dystrophy

Journal Article · Tue Aug 01 04:00:00 EDT 1995 · American Journal of Human Genetics

OSTI ID:105240

Bakel, I van; Holt, S; Craig, I ^[1]

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1. Univ. of Oxford (United Kingdom); and others

X;autosome translocations in females with Duchenne muscular dystrophy (DMD) provide an opportunity to study the mechanisms responsible for chromosomal rearrangements that occur in the germ line. We describe here a detailed molecular analysis of the translocation breakpoints of an X;autosome reciprocal translocation, t(X;5) (p21;q31.1), in a female with DMD. Cosmid clones that contained the X-chromosome breakpoint region were identified, and subclones that hybridized to the translocation junction fragment in restriction digests of the patient`s DNA were isolated and sequenced. Primers designed from the X-chromosomal sequence were used to obtain the junction fragments on the der(X) and the der(5) by inverse PCR. The resultant clones were also cloned and sequenced, and this information used to isolate the chromosome 5 breakpoint region. Comparison of the DNA sequences of the junction fragments with those of the breakpoint regions on chromosomes X and 5 revealed that the translocation arose by nonhomologous recombination with an imprecise reciprocal exchange. Four and six base pairs of unknown origin are inserted at the exchange points of the der(X) and der(5), respectively, and three nucleotides are deleted from the X-chromosome sequence. Two features were found that may have played a role in the generation of the translocation. These were (1) a repeat motif with an internal homopyrimidine stretch 10 bp upstream from the X-chromosome breakpoint and (2) a 9-bp sequence of 78% homology located near the breakpoints on chromosomes 5 and X. 32 refs., 4 figs., 2 tabs.

• OSTI ID: 105240
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 2 Vol. 57; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
GENE RECOMBINATION
GENES
GENETICS
GERM CELLS
HEREDITARY DISEASES
HUMAN CHROMOSOME 5
HUMAN X CHROMOSOME
NERVOUS SYSTEM DISEASES
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
RECESSIVE MUTATIONS