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PubMed1995

Assessing probability of paternity and the product rule in DNA systems.

The genetic resolution of paternity disputes begins with an intricate detection of inherited traits and finishes with a statistical inference (the probability of paternity, W). Notwithstanding some initial fanfare, statistical inference is a necessary component of DNA-based paternity tests because band patterns may be rare but not yet unique, and even rare events in a vacuum are meaningless. The genetic match must be combined with other evidence for relevancy, thus a Bayesian approach is preferred when computing W. This paper reviews the standard model used to compute W and discusses the model's various properties and assumptions. The standard model is extended to include DNA systems in which alleles are operationally continuous due to measurement error. This extension avoids problems associated with 'matched/non-matched' binned decisions. After outlining the model assumptions for a single DNA system, particular attention is given to the product rule-the procedure of multiplying intermediate probabilities across genetic loci to form a combined W. An empirical alternative to the product rule is also assessed and correlated with standard procedures.

Alleles↗
PubMed1993

Paternity testing with VNTR DNA systems. I. Matching criteria and population frequencies of the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11 in Danes.

Paternity testing using DNA polymorphism of variable numbers of tandem repeat (VNTR) regions with restriction fragment length polymorphism (RFLP) was implemented. HinfI-digested DNA was separated by electrophoresis in agarose gels and hybridized with radiolabelled probes detecting the VNTR-systems D2S44 (YNH24), D5S43 (MS8), D7S21 (MS31), D7S22 (g3), and D12S11 (MS43a). The intra gel variability of 970 duplicate investigations on the same gel of DNA from 122 individuals showed no differences exceeding 1.25 mm between the positions of the corresponding DNA fragments. The comparison of 1,624 DNA fragments from 342 mother/child pairs showed only one difference above 1.25 mm which was interpreted as a mutation. Based on these observations, we decided to consider an intra gel difference above 1.25 mm between the non-maternal DNA fragment of the child and the nearest DNA fragment of the putative father as an exclusion in paternity testing. This matching criterion was used for the comparisons of 1,197 DNA fragment differences in 247 pairs of children and putative fathers who had not been excluded by conventional marker systems. In all of these cases, the migration differences between the DNA fragments of non-excluded men and the DNA fragments of the children were less than 1.25 mm except in 6 cases (0.5%). The man/child differences in all of 227 false trios exceeded 1.25 mm in 2 or more of the 5 VNTR systems investigated. Matching criteria for inter gel comparisons in paternity testing were established. The frequency distribution of HinfI digested DNA fragments of the 5 VNTR systems in 650 unrelated Danes is presented and the raw data is available.

Adult↗
PubMed1979

Calculation of likelihood ratio y/x in diagnosis of paternity using computer methods.

A new computational method using a Monte Carlo technique is described for the calculation of plausibility of paternity in blood group systems. In this study gene frequencies of a blood group system are simulated by the range of the seven digit random numbers. By using a Monte Carlo method, four random numbers are generated and converted into paternal and maternal genotypes. Then the genotype of the child is determined according to the law of inheritance, and finally genotypes of the father, mother and child are converted into phenotypes. Repeating this process more than one hundred thousand times, the phenotypic frequencies of child-mother-father combinations (trio) and the likelihood ratio of paternity in any blood group system are calculated for all phenotypic combinations of the trios. This method is much easier than methods reported previously, and is sufficiently accurate.

Blood Group Antigens↗
PubMed1980

General formulas of the estimated likelihood ratio Y/X in the diagnosis of paternity of a deceased putative father.

When the putative father is dead his probable genotype, essential for estimate of likelihood ratio in the diagnosis of paternity, should be deduced from his relatives. In the present paper are described the general method for such deduction of probable genotype and the derivation of the formula of likelihood ratio. 10(4) examples of the diagnosis of paternity of deceased father are examined using a Monte Carlo method and the distributions of relative frequencies of log(Y/X) are calculated for the true father and non-father. These results indicate that the present method of estimation of Y/X from relatives is quite useful for the diagnosis of paternity of a deceased putative father.

Blood Group Antigens↗
PubMed2002

DXYS156: a multi-purpose short tandem repeat locus for determination of sex, paternal and maternal geographic origins and DNA fingerprinting.

In forensic science and in legal medicine Y chromosomal typing is indispensable for sex determination, for paternity testing in the absence of the father and for distinguishing males in multiple rape cases. Another potential application is the estimation of paternal geographic origin or family name from a crime stain to narrow down the range of suspects and thus reduce costs of mass screenings. However, Y typing alone cannot provide a sufficiently resolved DNA fingerprint as required for court convictions. Thus, there is a dilemma whether or not to sacrifice valuable material for the sake of extensive Y chromosomal investigations when stain DNA is limited (typically allowing only few PCR amplifications). We here describe a Y-chromosome-specific nucleotide insertion in the duplicate short tandem repeat (STR) locus DXYS156 which allows us to distinguish males from females as does the commonly used amelogenin system, but with the advantage that this locus is multi-allelic, thus substantially contributing towards DNA fingerprinting of a sample and furthermore enabling the detection of sample contamination. Yet another bonus is that both the X and the Y copies of DXYS156 have alleles specific to different parts of the world, offering separate estimates of maternal and paternal descent of that sample. We therefore recommend the inclusion of DXYS156 in standard multiplexing kits for forensic, archaeological and genealogical applications.

Base Sequence↗
PubMed2002

Paternity testing after pregnancy termination using laser microdissection of chorionic villi.

We report an unusual case of paternity testing from residues of chorionic villi 5 weeks after pregnancy termination. The autopsy of a 32-year-old female homicide victim revealed the presence of intact chorionic villi at the former placenta implantation site. Fetal cells were selectively isolated by laser-induced microdissection of the remaining villi to avoid contamination with maternal DNA. Simultaneous amplification of 12 STR loci in 2 PCR reactions resulted in a combined probability of paternity of 99.94%. This case demonstrates that laser-assisted microdissection and multiplex STR typing provide tools for paternity testing performed on endometrial mucosa long after the product of conception was removed by therapeutic abortion.

Abortion, Induced↗
PubMed2000

Molecular analysis of the human orosomucoid gene ORM1*Q0köln responsible for incompatibility in a German paternity case.

In a German paternity test, an alleged father was excluded only by reverse homozygosity of ORM1 phenotypes (mother ORM1 S, child ORM1 S and alleged father ORM1 F1) out of the 28 classical and DNA markers investigated. Without the ORM1 system the biostatistical probability of paternity was calculated to exceed 99.999%. The intensity of the immunoprinted bands of the ORM1 protein for the child and alleged father after isoelectric focusing appeared to be reduced to about half. To identify a possible null allele, gene-specific amplification followed by single-strand conformation polymorphism and sequencing analyses were carried out. Deletion of one of the two copies of a 4 bp direct repeat sequence (GTCT) in exon 4 of the consensus sequence of ORM1*F1 was observed in the child and alleged father. Thus, the sharing of a rare mutant gene, ORM1*Q0köln, increased the probability of paternity.

DNA Mutational Analysis↗
PubMed2003

[Paternalism in medicine: illustrated by the example of fiber optic bronchoscopy].

The question of when and how it is permissible for a physician to take a paternalistic approach to a patient is discussed. In the introduction, the physician-patient relationship is presented based on the empirical example of fiberbronchoscopy. An attempt to define the term paternalism more precisely leads to the result that not only are patients who are very limited in their autonomy (e.g. psychiatric and intensive-care patients) treated paternalistically, but that the patient status as such leads to a certain degree of paternalism. The example given is interpreted in detail and the pragmatic attitude of the physician to the patient "object" is criticized. Finally, a demand is made that the physician-patient relationship be a partnership, in which the physician appeals to the patient's autonomic components, addresses and encourages them. This latter approach is seen as an alternative to paternalism.

Adult↗
PubMed1993

Testosterone effects on paternal behavior and vasopressin immunoreactive projections in prairie voles (Microtus ochrogaster).

Castration reduced paternal responsiveness of male prairie voles (Microtus ochrogaster). Castration also reduced the number of vasopressin immunoreactive (AVP-ir) cells in the bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MA), as well as the density of AVP-ir fibers in the lateral septum. Testosterone treatment of castrated voles prevented these changes. The similarities in the effects of the hormonal manipulations on paternal responsiveness and AVP immunoreactivity provide further support for the hypothesis that AVP-ir projections of the BST and MA are implicated in paternal behavior.

Amygdala↗
PubMed1989

Prolactin and paternal behavior in the biparental California mouse, Peromyscus californicus.

Relatively little is known about hormonal mechanisms underlying paternal behavior in mammals. Male California mice, Peromyscus californicus, display extensive parental care toward their young. Parental behavior of fathers, expectant fathers (males living with their pregnant partner), and virgin males was assessed in a 10-min test with a 1- to 3-day-old alien pup. Few virgin males acted parental (19%) compared to fathers one day postpartum (80%) and expectant fathers (56%). Plasma prolactin levels were significantly elevated in fathers 2 days postpartum compared to expectant fathers and virgin males. Paternal prolactin levels were similar to those of mothers. There were no differences between groups in levels of plasma testosterone. These data suggest, contrary to other reports, that prolactin is a likely correlate of paternal behavior in rodents.

Animals↗
PubMed1995

Intrauterine growth retardation as an endpoint in mutation epidemiology: an evaluation based on paternal age.

Czeizel recently suggested that intrauterine growth retardation might be of value as a phenotypic endpoint in mutation epidemiology. We hypothesized that if some fraction of small-for-gestational age (SGA) births are due to new germinal mutations, then an association with advanced paternal age should be present. We evaluated the relation between paternal age and SGA, low birthweight, and preterm births using a large sample of births (n = 254,892) from North Carolina. The analyses were restricted to births of mothers aged 20-34 years and adjusted for maternal age, race, education, marital status, gravidity, and smoking. No material increase in the risk of SGA, low birthweight, and preterm delivery was found for fathers in any age category. For example, odds ratios for SGA ranged from 0.87 (fathers aged 50 years or greater) to 1.13 (fathers aged 45-49 years). The results indicate no discernable relationship between SGA and related endpoints and the increase in increase of mutations that accompany advanced paternal age.

Adolescent↗
PubMed1989

Justified paternalism in adolescent health care. Cases of anorexia nervosa and substance abuse.

This essay on the limits of adolescent autonomy espouses justified paternalism in adolescent medicine as a 1980s alternative to the "antipaternalistic" rights position of the 1970s. Thus, it proposes that the harm principle be a basis for justified limitations of liberty. In turn, justified paternalism should be both testable and severely limited because by definition it always involves treating someone in a way that violates a moral rule (e.g., coercive deprivation of freedom, invasion of privacy). Therefore, paternalism can only be justified when the evil prevented from occurring to the person is greater than the wrong caused by the violation of the moral rule and, more importantly, if it can be universally justified under relevantly similar circumstances always to treat persons in this way.

Adolescent↗
PubMed1991

Paternity testing--quo vadis?

The basis and efficiency of paternity testing using conventional markers (alloantigens or electrophoretically defined polymorphisms in blood) for individuals involved in cases of affiliation are shown. A possible use of DNA polymorphisms in paternity cases is discussed. Due to the fact that the formal genetics of DNA polymorphisms have not been fully validated by the analysis of large numbers of informative meioses, it is not yet possible to include these systems in routine paternity testing. As the vast majority of cases can be resolved by conventional markers, the inclusion of DNA polymorphisms is not usually necessary; in some cases, however, they can provide additional information.

DNA Fingerprinting↗
PubMedDate not supplied

Utility of HLA and six erythrocyte antigen systems in excluding paternity among 500 disputed cases.

Six erythrocyte antigen systems and the HLA system were evaluated to establish their practical value in 500 cases of disputed paternity. The actual results were very close to predicted values. HLA testing is expected to detect 92% and red cell testing is expected to detect 67% of men falsely accused in paternity suits. The findings of this study show that HLA detected 94% and red cell testing detected 69% of 107 men falsely accused in 500 paternity cases. In order of sensitivity, Rh, MNSs, and ABO were the most useful erythrocyte marker systems. There were six out of 107 cases in which exclusions would have been undetected if red cell typing had not been performed. Five of the six cases involved "common" HLA haplotypes.

ABO Blood-Group System↗
PubMed1984

How to select a satisfying typing program for paternity testing.

The efficiency of a typing program for paternity testing concerns three specific aspects: first, what is the percentage of non-fathers that cannot be excluded from paternity; second, what is the percentage of true fathers that cannot be recognized as probable fathers, and third, what is the percentage of non-fathers that will be assigned as probable fathers. When extensive materials for observation with any specific typing program are not directly available, only the chance of non-exclusion of non-fathers can be calculated in a relatively simple way. The aim of the present study was to find a relationship between this and the other two criteria. It was found that the variance of the distribution of natural logarithms of paternity index values is approximated rather well by the formula var. ln I = 0.65 X (n(ln 1/ne)2) (n = the number of genetic systems of the typing program and ne = the chance of non-exclusion of non-fathers). This allows the estimation of the two other critical percentages: the percentage of true fathers that cannot be assigned, and the percentage of non-fathers that will be assigned as probably true fathers.

Genetic Techniques↗
PubMed2004

The effect of advancing paternal age on pregnancy and live birth rates in couples undergoing in vitro fertilization or gamete intrafallopian transfer.

OBJECTIVE: This study was undertaken to determine effects of male aging on sperm parameters, fertilization, pregnancy, and live birth rates among in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) couples. The impact of female age was also investigated. STUDY DESIGN: Prospective study was made up of 221 IVF and GIFT couples. RESULTS: Pregnancy rates declined as the male subjects aged. Each additional year of paternal age was associated with 11% increased odds (P=.007) of not achieving a pregnancy, and 12% odds (P=.01) of not having a successful live birth. For first-time IVF/GIFT recipients, each additional year of paternal age was associated with a 5% increased odds of not achieving a pregnancy, whereas for repeaters it was 40% (P=.01). Advancing maternal age was associated with decreased numbers of oocytes retrieved or fertilized. Women 40 years or older compared with younger than 35 years had greater than 4-fold risk of not becoming pregnant, and greater than 20-fold risk of not achieving a live birth. CONCLUSION: Advancing paternal (and maternal) age had a deleterious effect on IVF and GIFT outcomes.

Adult↗
PubMed2004

Paternal age and the risk of birth defects in Norway.

PURPOSE: We studied 1,869,388 births from The Medical Birth Registry of Norway to assess the effect of father's age on risks of birth defects in offspring. METHOD: Thirteen separate categories were studied including pooled categories of neural tube defects and any type of defect. We used logistic regression models to adjust for maternal age, year of birth, maternity institution, parity, and correlation between siblings. RESULTS: There was little evidence of increased risk by high paternal age for any category of defects, except for a category of "other central nervous system" where risk estimates were 2.5-fold (95% CI: 1.2-5.5) for fathers aged between 45 and 49 years compared with the reference age group (25-29 years). The risk for neural tube defects was 1.3-fold (95% CI: 1.1-1.5) when the father was aged between 20 and 24 years relative to the reference. A pattern of moderately higher risks for younger fathers was consistent for anencephaly and spina bifida. Increased risk of heart defects was also estimated among children of young fathers. CONCLUSIONS: This study does not show consistent evidence that paternal ageing is a risk for birth defects among offspring. Low paternal age, or factors associated with younger parents, may however be associated with increased risk of neural tube defects in their offspring.

Adult↗
PubMed2006

Paternity in men with cystic fibrosis: a retrospective survey in France.

BACKGROUND: Because more patients reach adulthood, new questions as "what about having a child and/or paternity responsibility?" arose. METHOD: We performed a retrospective investigation based on the French CF registry. The context of the paternity and the health status of fathers were recorded. A comparison with clinical status of non-father patients and a compilation of follow-up data to evaluate its impact were done. RESULTS: Forty-eight men had 69 children. One fourth was said to be natural conceptions, 69% needed assisted reproduction techniques. No child had CF. Clinical status of men was satisfactory: mean BMI was 20.9 kg/m(2) and mean FEV(1) and FVC were 50.5% and 69.2% of predicted, respectively. When matched to CF non-fathers, few significant differences appeared. More non-fathers were F508del/F508del (p=0.03). Fathers' sputum cultures were positive for non-Pseudomonas aeruginosa strain (p=0.05), including Staphylococcus aureus (p=0.01). Mean age at diagnosis was higher, and based on minor evidence of sterility as first symptom leading to the diagnosis of CF (p=0.01) or aspergillosis (p=0.03). The 3-year follow-up showed no degradation of the clinical status. CONCLUSION: Men having paternity responsibility over children did not differ from the CF male population and neither did it seem to have an impact on the disease course.

Adult↗