PubMed Health⌕ Search

Biomedical subjects

S P Yip

Publications and source records attributed to S P Yip.

14 recordsLinked to original sources
PubMed2007

Phenotypic and population differences in the association between CILP and lumbar disc disease.

BACKGROUND: Lumbar disc disease (LDD) is one of the leading causes of disability in the working-age population. A functional single-nucleotide polymorphism (SNP), +1184T-->C, in exon 8 of the cartilage intermediate layer protein gene (CILP) was recently identified as a risk factor for LDD in the Japanese population (odds ratio (OR) 1.61, 95% CI 1.31 to 1.98), with implications for impaired transforming growth factorbeta1 signalling. AIM: To validate this finding in two different ethnic cohorts with LDD. METHODS: This SNP and flanking SNPs were analysed in 243 Finnish patients with symptoms of LDD and 259 controls, and in 348 Chinese subjects with MRI-defined LDD and 343 controls. RESULTS AND CONCLUSION: The results showed no evidence of association in the Finnish (OR = 1.35, 95% CI 0.97 to 1.87; p = 0.14) or the Chinese (OR = 1.05, 95% CI 0.77 to 1.43; p = 0.71) samples, suggesting that cartilage intermediate layer protein gene is not a major risk factor for symptoms of LDD in Caucasians or in the general population that included individuals with or without symptoms.

Cohort Studies↗
PubMed2004

Rapid detection of common southeast Asian beta-thalassemia mutations by nonisotopic multiplex PCR-SSCP analysis.

This report describes the detection of seven beta-thalassemia mutations common in Southeast Asia by amplifying three short PCR fragments in two separate tubes, followed by single-strand conformation polymorphism (SSCP) analysis in single lanes. These mutations are -28 A --> G, codon 17 A --> T, IVS1 + 5 G --> C, codon 41/42 -CTTT, codon 43 G --> T, codon 71/72 + A, and IVS2 + 654 C --> T, and account for 70% to over 95% of the cases in this region. This rapid nonisotopic method was also found capable of detecting other mutations within the amplified fragments. It is simple, rapid, and cheap, and thus suitable for carrier screening and prenatal diagnosis in Southeast Asia.

Asia, Southeastern↗
PubMed2003

Extent and distribution of linkage disequilibrium around the SLC11A1 locus.

The SLC11A1 (or NRAMP1) locus on human chromosome 2q35 encodes for the protein solute carrier family 11, member 1. It is expressed in macrophages and involved in the early stages of macrophage priming and activation. Different association studies have shown that the SLC11A1 gene affects susceptibility to infectious diseases and autoimmune inflammatory diseases. Although functional SLC11A1 polymorphisms may account for its role in affecting the susceptibility to these diseases, the positive association can also be because of flanking polymorphisms showing linkage disequilibrium (LD) with this locus. This is the first systematic study to investigate the LD pattern within and around the gene. LD was investigated by genotyping 17 genetic markers in a Chinese population (n=360). The results indicate that LD is maintained at least 110 kb both upstream and downstream of the locus. The complex LD pattern demands that association studies with SLC11A1 should be carried out with both 5' and 3' markers. The strong LD between IL8RB and the 5' SLC11A1 markers also dictates that IL8RB be tested for association with these diseases. Thus, positive association with SLC11A1 should be interpreted cautiously, and IL8RB should also be considered as a potential candidate susceptibility gene unless proven otherwise.

Alleles↗
PubMed2002

Sequence variation at the human ABO locus.

The ABO blood group is the most important blood group system in transfusion medicine. Since the ABO gene was cloned and the molecular basis of the three major alleles delineated about 10 years ago, the gene has increasingly been examined by a variety of DNA-based genotyping methods and analysed in detail by DNA sequencing. A few coherent observations emerge from these studies. First, there is extensive sequence heterogeneity underlying the major ABO alleles that produce normal blood groups A, B, AB and O when in correct combination with other alleles. Second, there is also extensive heterogeneity underlying the molecular basis of various alleles producing ABO subgroups such as A2, Ax and B3. There are over 70 ABO alleles reported to date and these alleles highlight the extensive sequence variation in the coding region of the gene. A unifying system of nomenclature is proposed to name these alleles. Third, extensive sequence variation is also found in the non-coding region of the gene, including variation in minisatellite repeats in the 5' untranslated region (UTR), 21 single nucleotide polymorphisms (SNPs) in intron 6 and one SNP in the 3' UTR. The haplotypes of these variations reveal a specific relationship with the major ABO alleles. Fourth, excluding the common alleles, about half of the remaining alleles are due to new mutations and the other half can better be explained by intragenic recombination (both crossover and gene conversion) between common alleles. In particular, the recombination sites in hybrid alleles can be quite precisely defined through haplotype analysis of the SNPs in intron 6. This indicates that recombination is equally as important as point mutations in generating the genetic diversity of the ABO locus. Finally, a large number of ABO genotyping methods are available and are based on restriction analysis, allele specific amplification, mutation screening techniques or their combinations.

ABO Blood-Group System↗
PubMed2002

Molecular genetic analysis of para-Bombay phenotypes in Chinese: a novel non-functional FUT1 allele is identified.

BACKGROUND AND OBJECTIVES: The para-Bombay phenotype (also known as H-deficient secretor) is characterized by a lack of ABH antigens on red cells, but ABH substances are found in saliva. Molecular genetic analysis was performed for five Chinese individuals serologically typed as para-Bombay. MATERIALS AND METHODS: ABO genotyping and mutational analysis of both FUT1 (or H) and FUT2 (or Se) loci were performed for these individuals using the polymerase chain reaction, single-strand conformation polymorphism analysis and direct DNA sequencing. RESULTS: The ABO genotypes of these para-Bombay individuals correlated with the types of ABH substances found in the saliva. Their FUT1 genotypes were h1h2 (three individuals), h2h2 (one individual) and h2h6 (one individual). Alleles h1 (547-552delAG) and h2 (880-882delTT) were known frameshift mutations, while h6 (522C > A) was a missense mutation (Phe174Leu) not previously reported. These three mutations were rare sequence variations, each with an allele frequency of less than 0.005. Phe174 might be functionally important because this residue is conserved from mouse to human. Their FUT2 genotypes were Se357se357,385 for the h2h6 individual and Se357Se357) for the others. Both FUT2 alleles were known: one functional (Se357) and one weakly functional (se357,385). That they carried at least one copy of a functional FUT2 allele was consistent with their secretor status. As FUT1 and FUT2 are adjacent on 19q13.3, there are three possible haplotypes in these para-Bombay individuals: h1-Se357; h2-Se357; and h6-se357,385. CONCLUSIONS: A novel non-functional FUT1 allele (522C > A, or Phe174Leu) was identified in a para-Bombay individual and on a se357,385 haplotype background.

ABO Blood-Group System↗
PubMed2000

Single-tube multiplex PCR-SSCP analysis distinguishes 7 common ABO alleles and readily identifies new alleles.

The ABO blood group is clinically the most important blood group system. Elucidation of the molecular basis of the ABO polymorphism allows genotype determination without family studies. Described here is a new method based on the simultaneous amplification by polymerase chain reaction (PCR) of 3 fragments from exon 6, and 5' and 3' ends of exon 7 of the ABO gene, followed by single-strand conformation polymorphism (SSCP) analysis. This multiplex PCR-SSCP protocol allows the well-established base changes at 9 nucleotide positions 261, 297, 467, 526, 646, 657, 681, 1059, and 1096 to be assayed simultaneously so that 7 common alleles (A(1), A(1v), A(2), B, O(1), O(1v), and O(2)) can be distinguished in a single-tube single-lane format. Each allele was characterized by a set of 3 haplotype-specific SSCP patterns. Chinese (n = 125) and white European (n = 98) samples were analyzed, and their genotypes were found consistent with the serologic phenotypes or could be deduced unambiguously. Fifteen samples (2 Chinese and 13 white European) were each found carrying at least 1 rare allele. Most of these alleles were new and some might be generated by intragenic recombination. This technique is the simplest, quickest, and most informative method reported to date and also readily identifies new alleles. (Blood. 2000;95:1487-1492)

ABO Blood-Group System↗
PubMed2000

The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic patients: multicentre retrospective study.

OBJECTIVE: To detect two novel mutations (C282Y and H63D) of the HFE gene in Chinese patients with hepatic iron overload. DESIGN: Multicentre retrospective study. SETTING: Four public hospitals, Hong Kong. PARTICIPANTS: Fifty Chinese patients who presented from January 1987 through December 1999 with hepatic iron overload from various causes. MAIN OUTCOME MEASURES: The DNA from liver biopsy samples was tested for HFE mutations by restriction fragment length polymorphism analysis. RESULTS: The sample DNA quality was unsatisfactory for analysis of the C282Y mutation in one case and the H63D mutation in nine cases. The C282Y mutation was not detected in any of the 49 satisfactory samples. Three of the 41 samples were heterozygous for the H63D mutation and only one was homozygous, giving an allele frequency of 6.1%. Of the three H63D-heterozygotes, one had beta-thalassaemia major, one had beta-thalassaemia minor, and one had hereditary spherocytosis. None of the 12 patients who were presumed to have primary haemochromatosis were positive for either mutation. CONCLUSIONS: The classical form of human leukocyte antigen-linked hereditary haemochromatosis appears to be absent form this locality. The H63D mutation is found in a minority (9.8%) of the patients, in whom it may act synergistically with an erythropoietic factor.

Adolescent↗
PubMed1999

Identification and characterisation of polymorphisms in human phosphoglucomutase (PGM1).

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 (theta) for PGM1 was estimated as 0.9 x 10(-3) based on 33 segregating sites in a sequence of 5187 nt and a sample size of 614 individuals.

Alleles↗
PubMed1999

Mapping recombination hotspots in human phosphoglucomutase (PGM1).

Human phosphoglucomutase (PGM1) is a highly poly-morphic 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 recombi-nation '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.

Alleles↗
PubMed1993

No association found between C3 alleles and scar hypertrophy.

Serum C3 was examined for structural variants using high-voltage agarose gel electrophoresis at both pH 6.2 and 8.4, thermal stability and stability to attack by hydroxyl radicals, in 450 Chinese people in Hong Kong. The C3 allele frequencies for electrophoretic variants were found to be 0.9911 for C3 *S and 0.0089 for all other rare alleles. No variants were found in terms of stability at 54 degrees C in the absence of Ca2+ or at 62 degrees C in the presence of Ca2+, and in terms of stability to attack by hydroxyl radicals. Based on a recently proposed single gene hypothesis for scar hypertrophy, statistical analyses were carried out to compare the relevant frequency data of scar hypertrophy with C3 phenotype frequencies, both for the local Chinese population and a European Caucasian population. There is no evidence for any association between C3 alleles or phenotypes and the formation of hypertrophic scars.

Cicatrix, Hypertrophic↗
PubMed1992

The effect of divalent metal ions on the thermostability of C3.

Thermostability studies on human complement component C3 showed that saturation of the electronegative sites in the C3 molecule with divalent cations offered some protection against heat denaturation, a finding not previously reported in the literature. To inactive C3 in about 30 minutes, the required temperature was 61 degrees C in the presence of excess Ca2+ ions, 59.5 degrees C in the presence of excess of Mg2+ ions, but only 54 degrees C in the absence of these ionized metal ions.

Calcium↗
PubMedDate not supplied

DNA polymorphism at the ABO locus in the Chinese population of Hong Kong.

DNA polymorphism at the ABO locus was investigated using denaturing gradient gel electrophoresis of polymerase-chain-reaction-amplified DNA products from 315 healthy individuals of the Chinese population of Hong Kong. Five different alleles were identified: ABO*O1, O2, A1, A2 and B1. The ABO*A2 is a new allele not previously reported in the literature. The allele frequencies found were 0.3698 for O1, 0.2508 for O2, 0.1952 for A1, 0.0159 for A2, and 0.1683 for B1. The Chinese population being investigated was in Hardy-Weinberg equilibrium. The genotyping method identifies many more alleles in the ABO locus and thus makes it a more useful genetic marker in linkage analysis, paternity testing and individualization in forensic work than when the locus is genotyped using conventional DNA-based methods or phenotyped using serological methods.

ABO Blood-Group System↗