Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients

Lawrence Reiter, Philip J. Hastings, Eva Nelis, Peter De Jonghe, Christine Van Broeckhoven, James R. Lupski

Research output: Contribution to journalArticle

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Abstract

The HNPP (hereditary neuropathy with liability to pressure palsies) deletion and CMT1A (Charcot-Marie-Tooth disease type 1A) duplication are the reciprocal products of homologous recombination events between misaligned flanking CMT1A-REP repeats on chromosome 17p11.2-p12. A 1.7-kb hotspot for homologous recombination was previously identified wherein the relative risk of an exchange event is 50 times higher than in the surrounding 98.7% identical sequence shared by the CMT1A-REPs. To refine the region of exchange further, we designed a PCR strategy to amplify the recombinant CMT1A-REP from HNPP patients as well as the proximal and distal CMT1A-REPs from control individuals. By comparing the sequences across recombinant CMT1A-REPs to that of the proximal and distal CMT1A-REPs, the exchange was mapped to a 557-bp region within the previously identified 1.7-kb hotspot in 21 of 23 unrelated HNPP deletion patients. Two patients had recombined sequences suggesting an exchange event closer to the mariner-like element previously identified near the hotspot. Five individuals also had interspersed patches of proximal or distal repeat specific DNA sequence indicating potential gene conversion during the exchange of genetic material. Our studies provide a direct observation of human meiotic recombination products. These results are consistent with the hypothesis that minimum efficient processing segments, which have been characterized in Escherichia coli, yeast, and cultured mammalian cells, may be required for efficient homologous meiotic recombination in humans.

Original languageEnglish (US)
Pages (from-to)1023-1033
Number of pages11
JournalAmerican Journal of Human Genetics
Volume62
Issue number5
DOIs
StatePublished - Jan 1 1998

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Charcot-Marie-Tooth Disease
Genetic Recombination
Homologous Recombination
Gene Conversion
Cultured Cells
Chromosomes
Yeasts
Observation
Escherichia coli
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients. / Reiter, Lawrence; Hastings, Philip J.; Nelis, Eva; De Jonghe, Peter; Van Broeckhoven, Christine; Lupski, James R.

In: American Journal of Human Genetics, Vol. 62, No. 5, 01.01.1998, p. 1023-1033.

Research output: Contribution to journalArticle

Reiter, Lawrence ; Hastings, Philip J. ; Nelis, Eva ; De Jonghe, Peter ; Van Broeckhoven, Christine ; Lupski, James R. / Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients. In: American Journal of Human Genetics. 1998 ; Vol. 62, No. 5. pp. 1023-1033.
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