TY - JOUR
T1 - Identification and characterisation of polymorphisms in human phosphoglucomutase (PGM1)
AU - Yip, Shea Ping
AU - Putt, W.
AU - Hopkinson, D. A.
AU - Whitehouse, D. B.
PY - 1999/3/1
Y1 - 1999/3/1
N2 - This study is part of our effort to map recombination hotspots in two regions (site A, 18 kb; site B, 40 kb) of the human phosphoglucomutase PGM1 gene. Twenty-two PCR amplified fragments comprising six groups, covering about 5.2 kb, were screened for single nucleotide polymorphisms (SNPs) using non-isotopic single stranded conformation polymorphism (SSCP) analysis. Fourteen fragments were variable and seven of these showed common polymorphism. Our strategy for screening for polymorphic sites in the PGM1 gene was based on the results of allelic association analysis between each new marker and the sites of the classical isozyme polymorphism (2/1 in exon 4 and +/- in exon 8). Samples from four populations (Caucasian, Chinese, Vietnamese and New Guinean) were typed for each of the seven polymorphic markers. Between two and four common alleles were found in each case, together with a few rare alleles. Co-dominant inheritance patterns were demonstrated by family studies. The molecular basis of each new marker was determined by direct sequencing of the PCR products: most were SNPs except two that were small insertions/deletions. Direct sequence analysis of a 2.1 kb segment in sixteen individuals revealed no additional nucleotide variation indicating a very high level of efficiency of the SSCP screening method used in this study. The overall nucleotide diversity (θ) for PGM1 was estimated as 0.9 x 10-3based on 33 segregating sites in a sequence of 5187 nt and a sample size of 614 individuals.
AB - This study is part of our effort to map recombination hotspots in two regions (site A, 18 kb; site B, 40 kb) of the human phosphoglucomutase PGM1 gene. Twenty-two PCR amplified fragments comprising six groups, covering about 5.2 kb, were screened for single nucleotide polymorphisms (SNPs) using non-isotopic single stranded conformation polymorphism (SSCP) analysis. Fourteen fragments were variable and seven of these showed common polymorphism. Our strategy for screening for polymorphic sites in the PGM1 gene was based on the results of allelic association analysis between each new marker and the sites of the classical isozyme polymorphism (2/1 in exon 4 and +/- in exon 8). Samples from four populations (Caucasian, Chinese, Vietnamese and New Guinean) were typed for each of the seven polymorphic markers. Between two and four common alleles were found in each case, together with a few rare alleles. Co-dominant inheritance patterns were demonstrated by family studies. The molecular basis of each new marker was determined by direct sequencing of the PCR products: most were SNPs except two that were small insertions/deletions. Direct sequence analysis of a 2.1 kb segment in sixteen individuals revealed no additional nucleotide variation indicating a very high level of efficiency of the SSCP screening method used in this study. The overall nucleotide diversity (θ) for PGM1 was estimated as 0.9 x 10-3based on 33 segregating sites in a sequence of 5187 nt and a sample size of 614 individuals.
UR - http://www.scopus.com/inward/record.url?scp=0032802265&partnerID=8YFLogxK
U2 - 10.1017/S0003480099007368
DO - 10.1017/S0003480099007368
M3 - Journal article
C2 - 10738524
SN - 0003-4800
VL - 63
SP - 129
EP - 140
JO - Annals of Human Genetics
JF - Annals of Human Genetics
IS - 2
ER -