Human Molecular Genetics, 1999, Vol. 8, No. 9 1699-1706
© 1999 Oxford University Press
Abstract |
Mapping recombination hotspots in human phosphoglucomutase (PGM1)
1MRC Human Biochemical Genetics Unit, Galton Laboratory, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK and 2Department of Nursing and Health Sciences, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
ABSTRACT
Human phosphoglucomutase (PGM1) is a highly polymorphic protein. Three mutations and four intragenic recombination events between the three mutation sites generate eight protein variants including the four universally common alleles, 1+, 1–, 2+ and 2–, and four others that are polymorphic in some Oriental populations, 3+, 3–, 7+ and 7–. The mutations 3/7, 2/1 and +/– are in exons 1A, 4 and 8, and are 40 and 18 kb apart, respectively. Using 12 polymorphic markers, including 2/1 and +/–, we have now obtained direct evidence for a high rate of intragenic recombination across this 58 kb region. From segregation analysis of PGM1 haplotypes in CEPH families, the recombination frequency was estimated to be 1.7%. We have also used a population genetics approach to map the patterns of linkage disequilibrium across the PGM1 gene in three diverse population samples (Caucasian, Chinese and Vietnamese). This has allowed us to compare indirect estimates of intragenic recombination with the meiotic data from family studies. Comprehensive pairwise allelic association analysis of the markers indicated the presence of two recombination ‘hotspots’: one between exons 1A and 4 and the other in the region of exon 7. These locations are in keeping with the meiotic data and with the original hypothesis of intragenic recombination based on PGM1 isozyme analysis.
FOOTNOTES
+ To whom correspondence should be addressed. Tel: +44 020 7504 5038; Fax: +44 020 7387 3496; Email: d.whitehouse{at}galton.ucl.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. A. Rana, N. D. Ebenezer, A. R. Webster, A. R. Linares, D. B. Whitehouse, S. Povey, and A. J. Hardcastle Recombination hotspots and block structure of linkage disequilibrium in the human genome exemplified by detailed analysis of PGM1 on 1p31 Hum. Mol. Genet., December 15, 2004; 13(24): 3089 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Schneider, T. E. A. Peto, R. A. Boone, A. J. Boyce, and J. B. Clegg Direct measurement of the male recombination fraction in the human {beta}-globin hot spot Hum. Mol. Genet., February 1, 2002; 11(3): 207 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hassold, S. Sherman, and P. Hunt Counting cross-overs: characterizing meiotic recombination in mammals Hum. Mol. Genet., October 1, 2000; 9(16): 2409 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Badge, J. Yardley, A. J. Jeffreys, and J. A. L. Armour Crossover breakpoint mapping identifies a subtelomeric hotspot for male meiotic recombination Hum. Mol. Genet., May 1, 2000; 9(8): 1239 - 1244. [Abstract] [Full Text] [PDF]
|
|