Estimation of myriad haplotype frequencies

Cj, MacLean; Ne, Morton

doi:10.1002/gepi.1370020304

Cited by 49 publications

(24 citation statements)

References 12 publications

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“…22 The frequency of the most frequent haplotypes was estimated by the maximum-likelihood method by using the MYRIAD program. 23 Hardy-Weinberg equilibrium was tested with a 2 test with 1 df. Genotype and allele frequencies were compared between cases and control subjects in the ECTIM Study and between groups defined in the AXA Study with a 2 test.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of the Human Matrix Gla Protein ( MGP ) Gene, Vascular Calcification, and Myocardial Infarction

Herrmann

Whatling

Brand

et al. 2000

ATVB

142

107

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Abstract-The matrix Gla protein (MGP) is an important inhibitor of vessel and cartilage calcification that is strongly expressed in human calcified, atherosclerotic plaques and could modulate plaque calcification and coronary heart disease risk. Using a genetic approach, we explored this possibility by identifying polymorphisms of the MGP gene and testing their possible association with myocardial infarction (MI) and plaque calcification. Eight polymorphisms were identified in the coding and 5Ј-flanking sequences of the MGP gene. All polymorphisms were investigated in 607 patients with MI and 667 control subjects recruited into the ECTIM Study (Etude Cas-Témoins de l'Infarctus du Myocarde) and in 717 healthy individuals with echographically assessed arterial calcification and atherosclerosis who were participating in the AXA Study. In the ECTIM Study, alleles and genotypes were distributed similarly in patients and controls in the whole study group; in only 1 subgroup of subjects defined as being at low risk for MI were the concordant AϪ7 and Ala 83 alleles more frequent in patients with MI than in controls (PϽ0.003). In the AXA Study among subjects with femoral atherosclerosis, the same alleles were more common in the presence than the absence of plaque calcification (PϽ0.025). The other MGP polymorphisms were not associated with any investigated clinical phenotype. Transient transfection experiments with allelic promoter-reporter gene constructs and DNA-protein interaction assays were carried out to assess possible in vitro functionality of the promoter variants detected at positions Ϫ814, Ϫ138, and Ϫ7 relative to the start of transcription. When compared with the Ϫ138 T allele, the minor Ϫ138 C allele consistently conferred a reduced promoter activity of Ϫ20% (PϽ0.0001) in rat vascular smooth muscle cells and of Ϫ50% (PϽ0.004) in a human fibroblast cell line, whereas the other polymorphisms, including Ϫ7, displayed no evidence of in vitro functionality. We conclude that the AϪ7 or Ala 83 alleles of the MGP gene may confer an increased risk of plaque calcification and MI; however, the observed relationships are weak or limited to subgroups of patients and therefore need confirmation. (Arterioscler Thromb Vasc

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Section: Discussionmentioning

confidence: 99%

Polymorphisms of the Human Matrix Gla Protein ( MGP ) Gene, Vascular Calcification, and Myocardial Infarction

Herrmann

Whatling

Brand

et al. 2000

ATVB

142

107

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“…Sci. USA 87 (1990) (25). The probability of linkage disequilibrium was calculated based on the x2 distribution of the Q statistic described by Hedrick et al (26).…”

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confidence: 99%

Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay.

Nickerson

Kaiser

Lappin

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

252

119

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DNA diagnostics, the detection of specific DNA sequences, will play an increasingly important role in medicine as the molecular basis of human disease is defined. Here, we demonstrate an automated, nonisotopic strategy for DNA diagnostics using amplification of target DNA segments by the polymerase chain reaction (PCR) and the discrimination of allelic sequence variants by a colorimetric oligonucleotide ligation assay (OLA). We have applied the automated PCR/OLA procedure to diagnosis ofcommon genetic diseases, such as sickle cell anemia and cystic fibrosis (AF508 mutation), and to genetic linkage mapping of gene segments in the human T-cell receptor f-chain locus. The automated PCR/OLA strategy provides a rapid system for diagnosis of genetic, malignant, and infectious diseases as well as a powerful approach to genetic linkage mapping of chromosomes and forensic DNA typing.

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“…Little and Rubin [23] provided a general description of the E-M algorithm for multinomial data. Hill [18], MacLean and Morton [26], Hawley and Kidd [17] and Chiano and Clayton [4] discussed different variations of the algorithm. Weir and Cockerham [36] suggested that in the case of two loci it is feasible to avoid iterations and obtained an explicit equation for the maximum likelihood estimate of gametic frequencies.…”

Section: Introductionmentioning

confidence: 99%

Testing Association of Statistically Inferred Haplotypes with Discrete and Continuous Traits in Samples of Unrelated Individuals

Zaykin¹,

et al. 2002

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There have been increasing efforts to relate drug efficacy and disease predisposition with genetic polymorphisms. We present statistical tests for association of haplotype frequencies with discrete and continuous traits in samples of unrelated individuals. Haplotype frequencies are estimated through the expectation-maximization algorithm, and each individual in the sample is expanded into all possible haplotype configurations with corresponding probabilities, conditional on their genotype. A regression-based approach is then used to relate inferred haplotype probabilities to the response. The relationship of this technique to commonly used approaches developed for case-control data is discussed. We confirm the proper size of the test under H₀ and find an increase in power under the alternative by comparing test results using inferred haplotypes with single-marker tests using simulated data. More importantly, analysis of real data comprised of a dense map of single nucleotide polymorphisms spaced along a 12-cM chromosomal region allows us to confirm the utility of the haplotype approach as well as the validity and usefulness of the proposed statistical technique. The method appears to be successful in relating data from multiple, correlated markers to response.

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Estimation of myriad haplotype frequencies

Cited by 49 publications

References 12 publications

Polymorphisms of the Human Matrix Gla Protein ( MGP ) Gene, Vascular Calcification, and Myocardial Infarction

Polymorphisms of the Human Matrix Gla Protein ( MGP ) Gene, Vascular Calcification, and Myocardial Infarction

Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay.

Testing Association of Statistically Inferred Haplotypes with Discrete and Continuous Traits in Samples of Unrelated Individuals

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