Molecular Cytogenetics: : PCR-based diagnosis of human trisomies using computer-assisted laser densitometry

Pena, Sérgio D.J.

doi:10.1590/s1415-47571998000300005

Cited by 11 publications

(15 citation statements)

References 16 publications

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“…It is possible to type microsatellites located near the chromosomal centromere (to avoid problems due to recombination) with the PCR using primers designed from the unique sequence DNA flanking the tandem repeat arrays, followed by quantitative analysis by computer-assisted laser densitometry (Pena, 1998). Microsatellite loci will be directly informative whenever they show more than one allele peak.…”

Section: Introductionmentioning

confidence: 99%

Testing and Estimating the Non‐Disjunction Fraction in Meiosis I using Reference Priors

et al. 2007

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SummaryIn this paper we analyze the fraction of non-disjunction in Meiosis I assuming reference (non-informative) priors. We consider Jeffreys's approach to built a non-informative prior (Jeffreys's prior) for the fraction of non-disjunction in Meiosis I. We prove that Jeffreys's prior is a proper distribution. We perform Monte Carlo studies in order to compare Bayes estimates obtained assuming Jeffreys's and uniform priors. We consider full Bayesian significance test (FBST) and Bayes factor (BF) for testing precise hypothesis on the fraction of non-disjunction in Meiosis I. The ultimate goal of this paper is to compare these two test procedures through simulation studies using both prior specifications. An application to Down Syndrome data is also presented.

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Section: Introductionmentioning

confidence: 99%

Testing and Estimating the Non‐Disjunction Fraction in Meiosis I using Reference Priors

et al. 2007

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“…The screening test developed by us is based on loss of heterozygosity and thus is not ideally suited for diagnosis of Turner syndrome after birth, since we could predict false negatives, even if we performed quantification of the microsatellite peaks by computer-assisted densitometry (Pena, 1998). However, due to its simplicity and quick results (less than 12 h when necessary), the multiplex X chromosome microsatellite test could be used as a preliminary screening when a rapid diagnosis of monosomy X is needed or desired, especially in the neonatal period.…”

Section: Discussionmentioning

confidence: 99%

“…With the utilization of computer-assisted laser densitometry it is possible to use polymerase chain reaction (PCR)-based tests to achieve the rapid, simple and inexpensive molecular diagnosis of human chromosomal disorders in non-dividing and even in non-living human tissues (Pena, 1998). Based on this, we developed a multiplex PCR procedure for the study of DNA extracted from tissues of fetal losses that effectively allows the establishment of the fetal sex and the diagnosis of triploidy and trisomies 13, 16, 18 and 21 in 100% of the cases examined (Pena, 1998). To increase the efficiency of this molecular cytogenetics procedure we needed to develop a molecular screening test for monosomy X, which is responsible for a sizeable proportion of fetal losses.…”

Section: Introductionmentioning

confidence: 99%

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Screening fetal losses for monosomy X with a simple PCR-based procedure

Pereira

Sturzeneker²,

Pena

2000

Genet. Mol. Biol.

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To screen for monosomy X in spontaneous fetal losses we explored a simple molecular strategy based on loss of heterozygosity at highly polymorphic X-linked loci. We developed a multiplex fluorescent procedure that allows the simultaneous amplification of five dinucleotide repeat polymorphisms in a large low-recombination region in the long arm of the X chromosome. Analysis was performed by computer-assisted laser densitometry. We did not find any instances of homozygosity at all five loci in 30 normal females tested, nor among 37 women whose typing data were retrieved from the Fondation Jean Dausset - CEPH genotype database. In addition, all cases of monosomy X previously diagnosed by conventional cytogenetics presented the anticipated loss of heterozygosity at all loci. We studied 19 spontaneously aborted female fetuses and we found four samples homozygous for the five loci (21%), in good agreement with the expected rate of monosomy X in first trimester spontaneous abortions. We conclude that the loci have high diversity and high efficiency in PCR-amplification and that our multiplex procedure constitutes a simple and useful molecular screening test for monosomy X in abortions and stillbirths.

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“…e model proposed in [16] considers that, using the PCR, it is possible to type microsatellites located near the chromosomal centromere (to avoid problems due to recombination) through primers designed from the unique DNA sequence �anking the tandem repeat arrays, followed by quantitative analysis by computer-assisted laser densitometry [17]. Trisomic patients will display, in informative microsatellite loci, three fragment peaks of equal intensity, 2 ISRN Genetics two fragments at an average 2 : 1 dosage, or one individual fragment (see an example of classi�cation in Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Reference Analysis in a Misclassification Model for the Meiosis I Nondisjunction Fraction in Trisomies

Loschi

Mayrink

2013

ISRN Genetics

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e determination of the meiosis I nondisjunction fraction plays an important role in identifying the characteristics of affected individuals and their mothers, which can generate aneuploidies. e number of individuals with one, two, and three peaks pattern is used to obtain the information; however, the data are susceptible to misclassi�cation. We review the misclassi�cation model previously introduced in the literature which considers a common misclassi�cation error. is paper aims to introduce a joint prior distribution for the meiosis I nondisjunction fraction and the misclassi�cation error. We prove that the reference prior is a proper distribution. We analyze a Brazilian Down syndrome dataset and compare the results with those obtained through Bayes-Laplace and beta prior distributions. IntroductionIn humans, aneuploidies are common causes of mental retardation, pregnancy losses, and fetal death. Although the causes of aneuploidies are unknown, it is known that the risk of having children with some kind of aneuploidy, such as trisomies 21 (Down syndrome), 18 (Edward's syndrome), or 13 (Patau syndrome), increases with the mother's age [1].Trisomy 21 is the most prevalent human genetic disorder and occurs in approximately 1 out of 700 births. It is the most common cause of mental retardation of genetic origin. Down syndrome affects the cognitive abilities of the child and approximately half of them can also have congenital heart defects and problems with hearing and vision, and they are prone to develop pulmonary hypertension. e causes of Down syndrome are unknown, but there is evidence that in the trisomy of chromosome 21 the rate of nondisjunction increases with the age of the mother [2]. Women aged 35 or older have signi�cantly higher risk of having a child with Down syndrome. In addition, the increase in the rate of non-disjunction in meiosis II is higher than in meiosis I, if the mother is between 35 and 39 years old. As a result, the determination of the fraction of non-disjunction in chromosomal segregation, taking place in meiosis I in each chromosome, plays an important role in understanding aneuploidies. It is useful to identify possible factors generating such abnormalities, for example: geography, nutrition, age, reproductive, practices. Prenatal diagnosis of aneuploidies is usually done by employing chromosome karyotype, �uo-rescent in situ hybridization (FISH), and polymerase chain reaction (PCR-) based approaches, see [1,[3][4][5][6] for further details.Methods to estimate considering information from the affected children and their parents are presented in [7][8][9][10][11][12][13][14][15] among others. More recently, Bayesian and classical approaches to infer about , assuming models that do not take into account the parental information, are presented in [2,16].e model proposed in [16] considers that, using the PCR, it is possible to type microsatellites located near the chromosomal centromere (to avoid problems due to recombination) through primers designed from the unique DNA sequence �an...

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Molecular Cytogenetics: : PCR-based diagnosis of human trisomies using computer-assisted laser densitometry

Cited by 11 publications

References 16 publications

Testing and Estimating the Non‐Disjunction Fraction in Meiosis I using Reference Priors

Testing and Estimating the Non‐Disjunction Fraction in Meiosis I using Reference Priors

Screening fetal losses for monosomy X with a simple PCR-based procedure

Reference Analysis in a Misclassification Model for the Meiosis I Nondisjunction Fraction in Trisomies

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