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Paternal age and risk of schizophrenia in adult offspring.

OBJECTIVE: The study examined the relation between paternal age at the time of birth and risk of schizophrenia in the adult offspring. METHOD: Data from the birth cohort of the Prenatal Determinants of Schizophrenia study were used in this study. Virtually all members of this birth cohort had prospective information about paternal age at the time of the offspring's birth. Subjects with schizophrenia and other schizophrenia spectrum disorders (N=71) among members of this birth cohort were previously ascertained. In separate analyses, paternal age was modeled as a continuous variable and as a categorical variable, and its relation with the risk of adult schizophrenia and other schizophrenia spectrum disorders and with the risk of schizophrenia separately were examined. RESULTS: There was a marginally significant, monotonic association between advancing paternal age and risk of adult schizophrenia and schizophrenia spectrum disorders. The association held after the analysis controlled for the effects of maternal age and other potential confounders. Similar results were observed when only subjects with schizophrenia were included in the analysis. CONCLUSIONS: Advanced paternal age at the time of birth of the offspring may be a risk factor for adult schizophrenia.

Adolescent↗

Spontaneous abortion, sex ratio, and paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

There is conflicting research regarding an association between fetal death and paternal exposure to Agent Orange, a phenoxy herbicide widely used in Vietnam that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Men who worked in the U.S. factories that produced Agent Orange were exposed to TCDD at levels hundreds of times higher than TCDD levels in the general population. Wives of TCDD-exposed chemical workers and wives of nonexposed neighborhood referents were interviewed to determine reproductive history. Paternal serum TCDD level at time of conception was estimated for each pregnancy using serum samples taken in 1987. Estimated TCDD levels of workers during or after exposure were high (median, 254 ppt; range, 3-16,340 ppt) compared to referent levels (median, 6 ppt; range, 2-19 ppt). No association between paternal TCDD level at the time of conception and spontaneous abortion was observed among pregnancies fathered by workers with TCDD levels of < 20 ppt [odds ratio (OR) = 0.77; 95% confidence interval (CI), 0.48-1.22], 20 to < 255 ppt (OR = 0.81; 95% CI, 0.40-1.63), 255 to < 1,120, (OR = 0.69; 95% CI, 0.30-1.58), and >or= 1,120 ppt (OR = 0.95; 95% CI, 0.42-2.17) compared to pregnancies fathered by referents. The sex ratio [males/(males + females)] of offspring also did not differ by TCDD exposure (0.53 and 0.54 among workers and referents, respectively). We did not find an association between paternal serum TCDD level and spontaneous abortion or sex ratio of offspring in this population. The estimated TCDD levels in this exposed worker population were much higher than in other studies, providing additional evidence that paternal TCDD exposure does not increase the risk of spontaneous abortion at levels above those observed in the general population. The study could not evaluate the effect of father's childhood or prenatal TCDD exposure on subsequent sex ratio.

Abortion, Spontaneous↗

DNA fingerprinting in relation to male dominance and paternity in a captive colony of tammar wallabies (Macropus eugenii).

The tammar wallaby has a polygynous mating system in which the dominant male usually controls initial access to oestrous females by mating first and then guarding the female from the advances of other subordinate males. In this study we used DNA fingerprinting with a human 3' hypervariable region (HVR) alpha globin probe to examine the paternity of pouch young progeny from 13 female tammars that were given continual access during the breeding season to a group of four sexually mature males. Constant individual-specific DNA profiles were observed for each animal. Paternity for 22 pouch young was successfully assigned using visual and computer-based analyses. However, no statistical difference was observed between the number of young sired by any of the four males (chi 2 = 2, d.f. = 3, P > 0.1). Mate guarding by the dominant male in our captive breeding group was not, therefore, sufficient to prevent successful subsequent matings by subordinates nor to enhance the genetic contribution of this male to the next generation. In each analysis, visual and computer assignments of paternity coincided, and these concurred with the results of a relatedness test which found that a large number of DNA bands were shared by sires and their progeny. The results from this paternity study show that first mating and subsequent mate guarding by the dominant male tammar wallaby in our captive group do not significantly skew the outcome of paternity towards this male and away from other males that subsequently mate with each female.

Animals↗

Paternal age as a risk factor for low birthweight.

OBJECTIVES: We examined associations between paternal age and low birth-weight in the US urban population. METHODS: Using a population-based sample of 4621 births, we used multiple logistic regression analysis to estimate associations between paternal age and low birthweight, controlling for maternal age, other demographic factors, and the child's gender. RESULTS: When the child's gender and the mother's race/ethnicity, birthplace, parity, marital status, and health insurance type were controlled, teenaged fathers were 20% less likely and fathers older than 34 years were 90% more likely than fathers aged 20 to 34 years to have low-birthweight babies. The associations were significant when maternal age was also controlled. No racial/ethnic differences in associations between paternal age and low birthweight were found. CONCLUSIONS: We identified paternal age as an independent risk factor for low birthweight in the US urban population, suggesting that more attention needs to be paid to paternal influences on birth outcomes and to the interactive effects of urban environments and individual risk factors on health.

Adolescent↗

Beyond medical paternalism and patient autonomy: a model of physician conscience for the physician-patient relationship.

Medical paternalism lies at the heart of traditional medicine. In an effort to counteract the effects of this paternalism, medical ethicists and physicians have proposed a model of patient autonomy for the physician-patient relationship. However, neither paternalism or autonomy are adequate characterizations of the physician-patient relationship. Paternalism does not respect the rights of adults to self-determination, and autonomy does not respect the principle of beneficence that leads physicians to argue that acting on behalf of others is essential to their craft. A model of physician conscience is proposed that summarizes the best features of both models--paternalism and autonomy.

Beneficence↗

The potential contribution of MVR-PCR to paternity probabilities in a case lacking a mother.

Minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) was applied to a paternity case lacking a mother to evaluate the paternity probability. After three flanking polymorphic sites at each of MS31A and MS32 loci were investigated from the child and alleged father, allele-specific MVR-PCR was performed using genomic DNA. It was confirmed that one allele in the child was identical to that in the alleged father at both loci. Mapped allele codes were compared with allele structures established from population surveys. No perfect matches were found although some motifs were shared with other Japanese alleles. The paternity index and probability of paternity exclusion at these two MVR loci were then estimated, establishing the power of MVR-PCR even in paternity cases lacking a mother.

Alleles↗

[Estimating probabilities and dealing with mutations in paternity testing--verification of DNA testing with commercially available STR kits].

Since Jeffreys devised a DNA fingerprint in 1985, DNA analysis has been applied to paternity testing. The progress of the techniques, especially the development of polymerase chain reaction (PCR), makes it possible to type 10-15 short tandem repeat (STR) loci in paternity testing by a single test tube. When using a well qualified database, we can now obtain a paternity index (PI) as high as 10(6) in usual trio cases. Furthermore, the DNA testings are now applied to unusual cases, such as personal identification of Japanese war orphans left in China. Here, we reviewed how to calculate the PI likelihood ratio and exclusion probability in a trio case, a motherless case, parent identification without reliable evidence of mother and child relationship, and a sibling case. We also reviewed how to handle single exclusion cases usually derived from a single mutation that is no longer rare when many STR loci are used. Finally, we emphasized the importance of ethical, legal and social counseling for clients in paternity testing. From that point of view, paternity tests by mail should not be allowed because of lack of such counseling.

Female↗

The relevance of paternity analysis in Romanian population using the D1S80 locus.

At present, DNA fingerprinting for human identification and paternity testing is a necessary and usual procedure. D1S80 is one of the best known polymorphic loci showing a VNTR, and exhibiting a high heterozygosity. This genetic locus, with a Tsp 509 I polymorphism of its 5' flanking sequence (1, 9), have been successfully amplified from human genomic DNA isolated from blood. The Tsp 509 I polymorphism was detected by restriction after PCR amplification. We tested the relevance of paternity analysis using the D1S80 locus considering the allele frequency distribution characteristic for our country. Paternal and maternal bands were compared with the children's DNA patterns. Our data include a comparison between D1S80 alleles amplified from mother, child and the supposed father for three tested families. This study was the first of this type made in Romania. We concluded a good power of discrimination and exclusion for this locus. It can be used successfully in the case of subtypes with low frequencies, and this is frequent for our population because of the high heterozygosity of D1S80 subtypes in Romanian population. We recommend the D1S80 use for exclusion paternity tests in Romanian population, as a very useful molecular tool, but we also recommend a complete set of molecular markers for confirmation paternity test in the same population.

Child↗

Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels.

BACKGROUND: Although paternal alcohol exposure has been shown to affect the growth and behavior of offspring, the mechanisms underlying these effects still remain to be elucidated. This study examines one possible mechanism, namely, altered genomic imprinting as reflected by changes in sperm cytosine methyltransferase messenger RNA (mRNA) levels. METHODS: Male rats were treated with alcohol for 9 weeks before breeding. Resulting fetuses were counted and weighed, and paternal sperm was examined for changes in cytosine methyltransferase mRNA levels. RESULTS: Alcohol did not affect mating, fecundity, or litter size, but it did result in significantly decreased mean fetal weight, increased fetal runt incidence in offspring, and decreased cytosine methyltransferase mRNA levels in paternal sperm, compared with pair-fed and ad libitum controls. CONCLUSIONS: Alcohol-induced reductions in cytosine methyltransferase mRNA levels may reflect altered genomic imprinting caused by reduced DNA methylation, which, in turn, may lead to the expression of normally silent paternal alleles and may be a mechanism for paternal alcohol effects.

Alcohol Drinking↗

[Possibilities of extension of blood group determination in cases of disputed paternity].

Results of the blood-group testing carried out in 1966-1974 in cases of discussed paternity are described in detail. Until 1970 only blood groups A1, A2, BO, MN and systems of Hp Rh and Gm (a) were tested (so called fundamental-testing). Maximal chance of exclusion of paternity on the base of these systems 70%. From 1970 on, the investigation have been extended to systems Gm (b), Gm(x), INV (1), Ss, Kell-Cellano, Duffy and during the last two years to systems of Gc, acid-phosphatase of erythrocytes and glutamat-pyruvat-transaminase. Thus the maximal chance of exclusion of paternity increased to 90%. Chances of exclusion on the base of every system are discussed separately also in detail. Fundamental-test were carried out in 10 200 cases, extended-tests in 278 cases. On the base of fundamental-tests exclusion of paternity could be achieved in 32, 85% of the cases. In 1974 in 374 (32, 21%) cases out of 1161 by fundamentaltesting, in further 100 (8,61%) cases by extended testing altogether in 474 (40,82%) cases- could be achieved exclusion of the paternity. These data indicate effectivity and reasonableness of the extension of blood-grouping-testing.

Blood Group Antigens↗

Assignment of paternity in a judicial dispute between two neighbor Holstein dairy farmers.

DNA profiling was used as evidence to assign paternity in a dispute between two neighbors in a judicial case of undue appropriation of cattle offspring from five alleged Holstein sires. Five offspring were genotyped using ten genetic markers (nine microsatellites and the BOLA-DRB3 locus). The computer program CERVUS was used to estimate the LOD score values and the confidence of paternity assignments. The results presented here show that three out of five paternity cases were assigned at 95% of confidence to a single sire with a LOD score ranging from 2.53 to 3.55. A fourth male was assigned using its delta value. Finally, all alleged sires were excluded from the paternity of the fifth offspring, probably due to the existence of an non-sampled male in the studied population. We concluded that the likelihood-based approach, included into CERVUS program, was a powerful tool in cattle kinship analysis when dealing with judicial dispute particularly when the dam's genotype was absent, allowing the assignments of paternity at 95% level of confidence in situations usually used by dairy and beef cattle producers in Argentine (e.g., multi-sire pasture mating).

Agriculture↗

Inverse relationship between age at onset of Huntington disease and paternal age suggests involvement of genetic imprinting.

It is well recognized that age at onset of Huntington disease (HD) is strongly influenced by the sex of the affected parent, and this has lead to suggestions that genetic imprinting or maternal specific factors may play a role in the expression of the disease. This study evaluated maternal and paternal ages, birth order, parental age at onset, and sex of the affected parent and grandparent in 1,764 patients in the National HD Roster by using linear-regression techniques which incorporated a weighted least-squares approach to accommodate the correlation among siblings. It was found that paternal age is negatively associated with age at onset of HD, particularly among subjects who inherit the mutant gene from grandfathers. Apparent associations between age at onset and birth order and between age at onset and maternal age were not significant after adjustment for paternal age. The paternal age effect is strongest among juvenile-onset cases and individuals with anticipation of greater than or equal to 10 years, although it is detectable across the entire age-at-onset distribution. The tendency for older fathers, including those not transmitting the HD gene, to have affected offspring with early-onset disease may be consistent with a gene imprinting mechanism involving DNA methylation. Because paternal age in unaffected fathers is also a significant determinant of age at onset, methylation in this context might involve HD modifier genes or the normal HD allele.

Adolescent↗

[HLA antigen typing in paternity disputes. Analysis of results].

Typing of 38-43 HLA antigens ruled out paternity in 33.75% of 726 men suspected, during 198 revisions in 71.72%. In 63.57% the man was ruled out concurrently in loci HLA-A and B incl. in 79.33% where the man and child had all HLA-A, B antigens different. Locus HLA-A alone was ruled out in 8.01%, locus HLA-B in 28.17%; in a single case the man was ruled out in locus HLA-C only. By family investigations the man was ruled out in three of 11 cases. In two cases of paternity of twins the man was ruled out from paternity only of one child. In one case superfecundation was involved, confirmed in systems Duffy, Inv, Hp, AP, in the second case the man was ruled out from paternity of the second child in the Hp system. Male carriers of antigens of haplotypes frequent in the population were not ruled out from paternity in high percentages: with HLA antigens A1, B8 in 37.19%, A2, B7 in 19.54%, A2, B12 in 24.72%, A3, B7 in 37.14%.

HLA Antigens↗

[The use of the erythrocyte adenylate kinase system in paternity suits].

Authors describe genetically determined polymorphisms, genetical feature and pattern of inheritance of the system of AK. Results and methods used in their studies first in the Hungarian population are reported. On the basis of examination of 1734 persons the incidence of the AK phenotypes was found as follows: AK 1 = 93,59%, AK 2 = 0,05%, and AK 2-1 6,34%. Values of gene frequency: AK1-0,9676, AK2-0,0322. According to the authors findings the maximal (theoretical) chance of the exclusion of paternity on the basis of AK system was 3,02%. In 844 cases of discussed paternity beside the investigation of the systems of A1A2BO, MN, Hp, Rh, Gm/a, x, b), InV(1), Gc, Ss, Kk, Fy(ab), VSP, PGM1, GPT and ADA the system of AK was also studied. In 191 cases (22,62%) the paternity could have been excluded. In 8 cases (0,94%) exclusion of the paternity have been based on the findings of the examination of AK system. In cases of discussed paternity authors recommend the examination of the AK system.

Adenylate Kinase↗

Establishing paternity using minisatellite DNA probes when the putative father is unavailable for testing.

A paternity case involving a putative father who had died a few years earlier in an automobile accident was referred to the laboratory for testing. The child and his mother, the deceased's parents, and nine of the deceased's siblings were available for analysis. As previously reported, paternity testing using red blood cell groups, human leukocyte antigens (HLA), red blood cell enzymes, serum proteins, and immunoglobulin allotypes gave a cumulative paternity index of 43,300 and a combined probability of paternity equal to 99.998%. RFLP analysis using Hinf I and Sau 3A single digests and the minisatellite deoxyribonucleic acid (DNA) probes 15.1.11.4 and 6.3 showed no exclusion of paternity and gave nearly conclusive evidence that the putative father was the biological father of the child.

DNA Probes↗

[The use of the adenosine desaminase (ADA) system in paternity cases].

Authors described genetically determined hereditary polymorphisms and pattern of inheritance of the adnosindesaminase (ADA) system. After a methodical review, results of their own investigations are reported, which were the first in the Hungarian population. The incidence of the ADA phenotypes among 1234 adult persons investigated was found: ADA-1=88%, ADA 2-1=11,58%, ADA 2=0,42%. Rare phenotypes were not detected. Values of gene frequency found: ADA1=0,93,79; ADA2= 0,0621; Results of the investigation of 561 mother-child pairs are also reported. The pattern of inheritance in every case examined was found to be regular. According to the author's data the maximal (theoretical) chance of the exclusion of paternity was 5,48%. In 561 cases of discussed paternity beside the examination of the systems of A1A2BO, MN, Ss, Hp, Rh, Gm(a,x,b), INV (1), Gc, Kk, Fy(a,b), SEP, PGM, GPT, and AK the ADA system was also examined. On the base of the last examinations the paternity could be excluded in 11 (1,97%) cases. In two cases (0,36%) exclusion of the paternity was based on the results of the examination of the ADA-system only. In the biostatistical evaluation of the results of examinations of blood-groups the role of the ADA system seems to be important. Examination of ADA system in cases of disputed paternity is recommended.

Adenosine Deaminase↗

A non-excluded set method for the calculation of paternity probability.

Forensic judgment of paternity depends on genetic and nongenetic evidence. Sometimes genetic marker tests can provide clear evidence to exclude a falsely accused man, but they do not always succeed. On the other hand, if the accusation is true, the alleged father will not ever be excluded by genetic marker tests. When a nonexclusion case occurs after one or more marker tests, a report of paternity probability is required in the court. The current methods for calculating the paternity probability are the "paternity index method" and the "nonexclusion method." A number of recent articles have openly debated the fallacies, validity and utility of both methods. This paper briefly reviews the two methods and proposes a non-excluded set method along with examples for illustrating the various patterns of paternity probabilities of the three methods.

Forensic Medicine↗

Microsatellite typing in a paternity case against a deceased man whose two brothers were available for testing.

To resolve a deficiency case of disputed paternity, we examined the mother, child, and two sibs of the deceased alleged father. In all of the 11 conventional marker systems and three microsatellite systems (ACTBP2, FGA, and D11S488) applied, the child and the paternal sibs had alleles is common. We deduced first the possible ACTBP2 genotypes of the deceased parents of the two sibs from their test results. Next, from all the combinations of the deduced genotypes, we estimated the frequencies of the possible genotypes of the alleged father and, with Bayes' theorem, calculated the probabilities of the alleged father having the genotypes compatible with paternity. Using these probabilities, we worked out the probability of the child's genotype resulting from the mating of the mother with the alleged father. Meanwhile, we calculated the probability of the child's genotype being expected of the mating of the mother with an unrelated random man. Finally, applying Bayes' theorem again, we obtained a probability of paternity of 0.992 for the ACTBP2 locus alone. Inclusion of the FGA locus in the probability calculations brought the overall probability of paternity to 0.998. The present study demonstrates that testing for hypervariable microsatellite loci greatly facilitates the solution of a deficiency case that would be difficult or time-consuming to solve by conventional marker typing.

Female↗