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Advancing paternal age and autism.

CONTEXT: Maternal and paternal ages are associated with neurodevelopmental disorders. OBJECTIVE: To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD). DESIGN: Historical population-based cohort study. SETTING: Identification of ASD cases from the Israeli draft board medical registry. PARTICIPANTS: We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses. MAIN OUTCOME MEASURES: Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental age data. RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

Adult↗

Excess paternal age in apparently sporadic osteogenesis imperfecta.

The objective of this study was to examine whether parental age is associated with the occurrence of apparently sporadic osteogenesis imperfecta (OI). We compared parental age and the joint distribution of maternal and paternal age with expected distributions based on statutory birth records for each year and location of birth. The study included patients with OI based in the United Kingdom. The study was restricted to cases born in England, Wales, and Scotland between 1961 and 1998. Subgroup analysis was by clinical type [Sillence et al., 1979: J Med Genet 16:101-116] and apparent mode of inheritance based on pedigree analysis. Of 730 eligible cases, 357 were apparently sporadic. The mean age of fathers at birth of children with apparently sporadic OI was 0.87 years greater than expected (P = 0.010; 95% confidence interval = 0.21 to 1.54 years). The relative risk was 1.62 for fathers in the highest quintile of paternal age compared with fathers in the lowest quintile. The magnitude of the paternal age excess did not differ significantly between Sillence types (analysis of variance P = 0.534). In sporadic cases, paternal age was 0.51 years greater than expected, given maternal age, year, and location of birth (P = 0.033). In contrast, in familial cases, there was no significant paternal age excess, and paternal age was not significantly different from that expected given maternal age. Increased paternal age is a significant risk factor for sporadic OI. This effect is not accounted for by increasing maternal age. The magnitude of the paternal age excess is small in comparison with that in some other autosomal dominant disorders.

Adult↗

A case of segmental paternal isodisomy of chromosome 14.

Uniparental disomy of chromosome 14 (UPD 14) results in one of two distinct abnormal phenotypes, depending upon the parent of origin. This discordance may result from the reciprocal over-expression and/or under-expression of one or more imprinted genes. We report a case of segmental paternal isodisomy for chromosome 14 with features similar to those reported in other paternal disomy 14 cases. Microsatellite marker analysis revealed an apparent somatic recombination event in 14q12 leading to proximal biparental inheritance, but segmental paternal uniparental isodisomy distal to this site. Analysis of monochromosomal somatic cell hybrids containing either the paternally inherited or the maternally inherited chromosome 14 revealed no deletion of the maternally inherited chromosome 14 and demonstrated the presence of paternal sequences from D14S121 to the telomere on both chromosomes 14. Thus, the patient has paternal isodisomy for 14q12-14qter. Because the patient shows most of the features associated with paternal disomy 14, this supports the presence of the imprinted domain(s) distal to 14q12 and suggests that the proximal region of chromosome 14 does not contain imprinted genes that contribute significantly to the paternal UPD 14 phenotype.

Abnormalities, Multiple↗

Distinguishing minisatellite mutation from non-paternity by MVR-PCR.

Minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) was devised to map the interspersion pattern of subtle variant repeats along minisatellite tandem arrays. MVR-PCR has revealed enormous diversity of allele structures at several loci, far more than can be resolved by allele length analysis. We have reported the application of MVR-PCR at minisatellite MS32 (D1S8) and MS31A (D7S21) in a paternity case lacking a mother and showed that it resulted in higher paternity probabilities than for a set of 12 other DNA markers including six STRs. Hypervariable minisatellites like MS32 and MS3lA can however, show significant germline mutation rates to new length alleles which can generate false exclusions in paternity cases although paternity cases showing mutant paternal alleles at more than one locus will be rare when several MVR loci are examined. Detailed knowledge of mutation processes coupled with MVR analysis of allele structure can help distinguish mutation from non-paternity. We now show how similar mutant alleles are to their progenitors using both real and simulated data, and demonstrate how MVR-PCR can be used to identify mutant paternal allele in paternity cases showing apparent exclusions.

Bias↗

Is male-infant caretaking related to paternity and/or mating activities in wild Barbary macaques (Macaca sylvanus)?

In species with a promiscuous mating system, the functions of male-infant caretaking remain unclear in the absence of genetic paternity tests. We tested paternal investment and hypotheses concerning reproductive tactics in wild groups of Barbary macaques, including results of genetic paternity tests. Our study revealed that male-infant caretaking was not related to the probability of paternity. In principle, males could use access to females to estimate paternity. However, we found that mating success was not related to paternity, so males could invest in infants that they had not sired, and caretaking of non-offspring was actually observed. Accordingly, males might be 'deceived' with respect to their paternal investment. In that case, one would expect a positive relation between mating success and the subsequent rate of male caretaking of infants. Such a relation is also lacking, leading to comprehensive rejection of the paternal investment hypothesis in Barbary macaques. By contrast, there was evidence that males showing infant care achieved higher mating frequencies than other males with the mothers of the relevant infants. Thus, male Barbary macaques do not show a 'mate-then-care' pattern, but they do exhibit a 'care-then-mate' pattern.

Animals↗

Child support enforcement program: paternity establishment and revision of child support enforcement program and audit regulations--Office of Child Support Enforcement. Final rule.

This final rule contains provisions regarding both paternity establishment and the audit. The paternity establishment provisions implement the requirements of section 13721 of the Omnibus Budget Reconciliation Act of 1993 (OBRA '93) signed by the President on August 10, 1993, which amends title IV-D of the Social Security Act (the Act). These provisions require States to adopt procedures for a simple civil process for the voluntary acknowledgement of paternity, including early paternity establishment programs in hospitals. For paternity cases that remain contested, the statutory provisions require States to adopt a variety of procedures designed to streamline the paternity establishment process. These include the use of default orders, a presumption of paternity based on genetic test results, conditions for admission of genetic test results as evidence, and expedited decision-making processes for paternity cases in which title IV-D services are being provided. In addition, this final regulation amends the Child Support Enforcement program regulations governing the audit of State Child Support Enforcement (IV-D) programs and the imposition of financial penalties for failure to substantially comply with the requirements of title IV-D of the Act. This regulation specifies how audits will evaluate State compliance with the requirements set forth in title IV-D of the Act and Federal regulations, including requirements resulting from the Family Support Act of 1988 and section 13721 of OBRA '93. This final regulation also redefines substantial compliance to place greater focus on performance and streamlines Part 305 by removing unnecessary sections.

Child Welfare↗

[Paternity analysis using four DNA markers amplified by polymerase chain reaction].

BACKGROUND: DNA typing in forensic analysis is a useful tool to analyze paternity due to its high discrimination power. AIM: To report the experience of Servicio Medico Legal in Santiago, resolving cases of dubious paternity. SUBJECTS AND METHODS: Four highly polymorphic loci, amplified by polymerase chain reactions, were analyzed in 153 cases of uncertain paternity. The paternity index was calculated for each case. RESULTS: The four genetic markers analyzed provided an exclusion probability of 0.933 for the general population in Santiago. Thirty-seven cases were excluded as parents. In 31 cases, the paternity index ranged from 19 to 100, considered as probable paternity and 77 cases had an index of over 100, considered as almost certain paternity. Eight cases had an index between 0.5 and 19, considered as inconclusive. All loci met Hardy-Weinberg expectations and their frequencies were similar to other data from people living in Santiago. CONCLUSIONS: The use of these genetic markers proved to be very useful, reliable and with a high exclusion power for paternity analysis.

DNA↗

Social and environmental factors influence the suppression of pup-directed aggression and development of paternal behavior in captive meadow voles (Microtus pennsylvanicus).

During summer, female meadow voles (Microtus pennsylvanicus) maintain territories and males do not engage in paternal care. As day length shortens, territories dissolve and males nest with females and young. Because paternal behavior has never been studied in free-living meadow voles during colder months or in the laboratory under short photoperiods, the authors examined whether males housed in short day (SD) lengths exhibited more frequent or better quality paternal behavior than males housed in long day (LD) lengths. Sexually and parentally inexperienced (naive) SD males exhibited proportionally more and qualitatively better paternal care than naive LD males. SD males were more responsive than LD males to classic social cues associated with prepartum aggression inhibition and paternal onset. SD sires also displayed qualitatively better paternal behavior than LD sires. These data suggest that meadow vole paternal state is regulated by specific social and environmental cues that may contain reliable information about ecological conditions that favor paternal care.

Aggression↗

[Evaluation on the number and value of STR loci applied in paternity identification].

OBJECTIVE: The study was carried out on the evaluation of number and value of STR loci applied in paternity identification. METHODS: A total of 13 STR loci, divided into four groups, was observed in 102 cases of paternity exclusion and 100 cases of paternity inclusion. PCR amplified products of 13 STR loci were injected into a capillary on the ABI PRISM 310 Genetic Analyzer. GeneScan software analyzed the collected data, which can then be imported into Genotyper software for genotyping of alleles. RESULTS: At least 3 STR loci incompatibilities between alleged father and child were found in all paternity exclusion cases of two observed groups which Cumulative Probability of Exclusion (CPE) was more than 99.99%, and in all paternity inclusion cases of those same observed groups, their Relative Chance of Paternity(RCP) could be over 99.99%. CONCLUSION: The exclusion of paternity should be based on at least three STR loci incompatibilities in the identification practice. As a criterion for evaluation of the number and value of STR loci applied in paternity test, CPE should reach 99.99%.

Adult↗

Paternal age: are the risks of infecundity and miscarriage higher when the man is aged 40 years or over?

BACKGROUND: Maternal age of 35 years or over is a well-known risk factor for human reproduction that has been extensively investigated by demographers and epidemiologists. However, the possibility of a paternal age effect has rarely been considered. We carried out review of the literature to investigate the effect of paternal age on the risks of infecundity and miscarriage. METHODS: We carried out a MEDLINE search and checked the exhaustiveness of our reference list. RESULTS: We identified 19 articles analysing the effect of paternal age. Epidemiological studies provided evidence that paternal age older than 35-40 years affects infecundity. However, the few studies based on data from assisted reproductive techniques (especially IVF with ovum donation) do not confirm this finding. All studies analysing the effect of paternal age on the risk of miscarriage showed an increased risk in men aged 35-40 years or over. Other studies have shown some evidence for a paternal age effect on late foetal deaths. CONCLUSION: The risks of infecundity and miscarriage increase with paternal age. Two main hypotheses can be considered. First, these risks increase after the age of 35-40 years. However, a later paternal age effect (after 45-50 years) cannot be excluded. Second, due to the interaction of the ages of the two partners, the risks of infecundity and miscarriage may be higher when both partners are older (woman aged 35 years or over and man aged 40 years or over).

Abortion, Spontaneous↗

[Forensic hematology genetics--paternity testing].

In Switzerland paternity investigations are carried out using DNA analysis only since 1991. DNA patterns are inherited and only with the exception of genetically identical twins they are different in everyone and therefore unique to an individual. Hence DNA-systems are an excellent tool to resolve paternity disputes. DNA polymorphisms used for paternity diagnosis are length polymorphisms of the highly polymorphic VNTR loci [variable number of tandem repeats]. The most frequently applied systems are the DNA single locus systems. In addition to the DNA single locus systems the application of PCR (PCR = polymerase chain reaction) based DNA systems has increased particularly in difficult deficiency cases or in cases where only small evidential samples or partially degraded DNA are available. Normally four independent DNA single probes are used to produce a DNA profile from the mother, the child and the alleged father. A child inherits half the DNA patterns from its mother and the other half from its true biological father. If an alleged father doesn't possess the paternal specific DNA pattern in his DNA profile he is excluded from the paternity. In case of non-exclusion the probability for paternity is calculated according to Essen-Möller. When applying four highly polymorphic DNA single locus systems the biostatistical evaluation leads always to W-values exceeding 99.8% [= required value for positive proof of paternity]. DNA analysis is currently the best available method to achieve such effective conclusions in paternity investigations.

Blood Group Antigens↗

[Paternity analysis: experience in Colombia].

BACKGROUND: Cases of dubious paternity may be resolved analyzing appropriate genetic markers in them. AIM: To report the experience of a Colombian University in resolving cases of dubious paternity. SUBJECTS AND METHODS: Fourteen serologic and electrophoretic genetic markers, that had a high probability of exclusion were analyzed in 349 cases of uncertain paternity. RESULTS: In 50 cases, paternity was excluded and in 34, paternity was attributed with a probability over 0.99. In 85 cases, the paternity index was between 19 and 100, that classifies paternity as probable and in 179 cases, the analysis was inconclusive. CONCLUSIONS: These genetic markers may be useful in the first approach to a paternity in investigation.

Colombia↗

Basic fallacies in the formulation of the paternity index.

Some basic fallacies in the computation of the paternity index have been pointed out. The general finding that the true fathers' mean paternity index is greater than that of nonfathers is a necessary consequence of an algebraic identity, having nothing to do with paternity or nonpaternity. It has also been shown that the paternity index is not a likelihood ratio as claimed. The fact that a paternity index may frequently take values less than unity leads to absurd conclusions regarding the probability of paternity. A formula relating prior and posterior probabilities of paternity, based solely on genetic marker testing results (exclusion or nonexclusion), is reiterated as a substitute for the current paternity index.

Humans↗

Colour bands, mate choice and paternity in the bluethroat.

Studies of several bird species have shown that coloured leg bands may affect a male's success in mate attraction and/or mating competition. From a colour band experiment in the field, we have previously reported that male bluethroats, Luscinia s. svecica, with blue and orange bands (BO males) guarded their mates less intensely at the peak of female fertility, and spent more time advertising for additional mates, than males banded with non-BO colours. These responses indicated that BO males experienced less threat to their paternity than did non-BO males, possibly mediated through an increased attractiveness. Here we present paternity analyses of the broods from the field study and test whether there were differences between the two male groups in within-pair or extrapair paternity. There were no significant differences between the two groups of males in paternity, suggesting effective male protection of paternity. However, extrapair paternity was infrequent in the 2 years of the field experiment; hence, the power in detecting effects on paternity does not allow a definitive conclusion on this issue. We also conducted an aviary experiment in which females were given the choice between a BO male and a non-BO male, to test whether females had preferences for particular colour bands. Females did not associate more with BO males, as would have been expected if these males were more attractive in social mate choice. Our results suggest that the effects of colour bands on social mate choice and paternity are, at best, weak. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗

Identification of paternal mitochondrial DNA sequences in the nucleus-cytoplasm hybrids of tetraploid and hexaploid wheat with D and D2 plasmons from Aegilops species.

Mitochondrial (mt) DNA structures were studied in 12 nucleus-cytoplasm (NC) hybrids of tetraploid and hexaploid wheat in which nuclear genomes of the recurrent paternal wheat parents were combined with D and D2 plasmons from Aegilops species. RFLP analysis of 15 mtDNA regions indicated the presence of the paternal sequences in six regions encompassing 11 structural genes in all the NC hybrids. PCR-RFLP analysis showed that one region (a nad3-orf156 region) consisted of a mixture of the maternal, paternal and novel paternal-like sequences. The presence of unexpectedly high levels of the paternal sequences was confirmed by random PCR cloning and sequencing of this region. PCR-RFLP analysis of the random clones further showed that the relative stoichiometry of the maternal and paternal sequences varied depending on the plasmons from the maternal parents and the nuclear backgrounds of the paternal parents. Our results suggest that the differential amplification of the paternal mtDNA sequences is under the control of NC interaction in these NC hybrids.

Base Sequence↗

Pregnancy can induce long-persisting primed CTLs specific for inherited paternal HLA antigens.

Previous studies showed that pregnancy can prime the maternal cellular immune response directed against paternal HLA antigens. Primed CTLs specific for inherited paternal HLA antigens (IPA) were found in women who had formed HLA allo antibodies, whereas naive CTLs were present in women who did not form antibodies against the paternal HLA antigens. As HLA allo antibodies may disappear in time, it is not clear which women on the waiting list for transplantation have been sensitized to paternal HLA antigens and are at risk for graft rejection if paternal HLA antigens are shared by the donor organ. The presence of primed CTLs specific for a particular antigen is considered to be a reflection of sensitization.In the present study we investigated whether these primed CTLs persist in women who had been pregnant and had formed antibodies against the inherited paternal HLA class I antigens. For this purpose 14 women who had their last pregnancy 10 years ago were analyzed with respect to IPA-specific CTLp frequencies and the presence of high avidity CTLs directed against inherited paternal HLA class I antigens. Although primed CTLs specific for IPA's were found more frequently in women with persisting alloantibodies, they still can be detected when the antibodies have disappeared. The current data show that primed CTLs directed against inherited paternal HLA antigens towards which antibodies have been formed in the past can persist for more than 10 years after pregnancy. The cellular test used in our study can be useful to detect presensitization in women with a history of pregnancy, who enter the waiting list for transplantation.

Female↗

Lymphocytotoxins in sera from highly sensitized multiparous dialysis patients: antibody class, relationship with the HLA and with paternal antigens.

1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70% of a panel of lymphocytes from 24 donors (panel reactivity greater than 70%). 2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens. 3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50% of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80% was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens. 4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class. 5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies. 6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to antigens in blood transfusions from donors who share paternal class I specificities.

Adult↗

Paternity after bilateral vasectomy.

OBJECTIVES: To determine whether the occurrence of recanalization depends on the technique of vasectomy. MATERIALS AND METHODS: A survey was conducted among Dutch urologists using a questionnaire in which information was gathered about the surgical procedure, postoperative complications, results of semen analysis after vasectomy, time between vasectomy and occurrence of paternity, results of semen analysis after paternity, performance of revasectomy, results of histological examination of the revasectomy specimen and whether the event had changed the protocol of the urologists. RESULTS: In all, 32 cases of paternity after vasectomy were registered. Surgical techniques and the criteria for a successful vasectomy differed among the responding urologists. There was a difference in time to paternity between men who did and did not correspond with the criteria. In most cases, semen analysis after paternity showed numerous motile sperm. Six men initiated litigation after paternity and the vasectomy protocol was modified by five urologists. CONCLUSION: Paternity consequent on recanalization can occur at any time after bilateral vasectomy and does not depend on the surgical procedure or criteria for sterility. Because of the major consequences of paternity after vasectomy for both the man and urologist, accurate information about the possibility of recanalization should be given to the man beforehand.

Fertilization↗