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PubMed2004

Genetic origins of the Ainu inferred from combined DNA analyses of maternal and paternal lineages.

The Ainu, a minority ethnic group from the northernmost island of Japan, was investigated for DNA polymorphisms both from maternal (mitochondrial DNA) and paternal (Y chromosome) lineages extensively. Other Asian populations inhabiting North, East, and Southeast Asia were also examined for detailed phylogeographic analyses at the mtDNA sequence type as well as Y-haplogroup levels. The maternal and paternal gene pools of the Ainu contained 25 mtDNA sequence types and three Y-haplogroups, respectively. Eleven of the 25 mtDNA sequence types were unique to the Ainu and accounted for over 50% of the population, whereas 14 were widely distributed among other Asian populations. Of the 14 shared types, the most frequently shared type was found in common among the Ainu, Nivkhi in northern Sakhalin, and Koryaks in the Kamchatka Peninsula. Moreover, analysis of genetic distances calculated from the mtDNA data revealed that the Ainu seemed to be related to both the Nivkhi and other Japanese populations (such as mainland Japanese and Okinawans) at the population level. On the paternal side, the vast majority (87.5%) of the Ainu exhibited the Asian-specific YAP+ lineages (Y-haplogroups D-M55* and D-M125), which were distributed only in the Japanese Archipelago in this analysis. On the other hand, the Ainu exhibited no other Y-haplogroups (C-M8, O-M175*, and O-M122*) common in mainland Japanese and Okinawans. It is noteworthy that the rest of the Ainu gene pool was occupied by the paternal lineage (Y-haplogroup C-M217*) from North Asia including Sakhalin. Thus, the present findings suggest that the Ainu retain a certain degree of their own genetic uniqueness, while having higher genetic affinities with other regional populations in Japan and the Nivkhi among Asian populations.

Asian People↗

PubMed2005

Childhood cancer and social contact: the role of paternal occupation (United Kingdom).

OBJECTIVE: To investigate the relationship between childhood cancer (particularly leukaemia) and paternal occupational social contact (a proxy for potential exposure to infections) using the UK Childhood Cancer Study. METHODS: Using a national population-based case-control study, self-reported occupational data from fathers of 3596 children diagnosed with cancer between 1991 and 1996 under 15 years of age (cases) and fathers of 7011 children without cancer (controls) were analysed. Associations were assessed using odds ratios (OR) calculated by time of exposure (birth, diagnosis), diagnostic group (all cancers, leukaemia, acute lymphoblastic leukaemia (ALL), central nervous system tumours, other cancers), level of occupational social contact (high, medium, low), urban-rural status at diagnosis and occupational title. RESULTS: From 371 occupations, 75 (20%) were classified as having high levels of occupational social contact, 31 (8%) as medium and the remaining 265 (71%) as low. No associations were apparent for fathers' occupational social contact overall, for any time period or diagnostic group. OR for leukaemia and high levels of paternal occupational social contact at birth and diagnosis being 1.02 (95% confidence interval (CI) = 0.88-1.18) and 0.91 (95% CI = 0.79-1.06), respectively. Analyses by urban-rural status at diagnosis and by occupational title revealed no notable associations. CONCLUSIONS: The analyses of paternal occupational histories do not support the suggested association between high levels of paternal occupational social contact and an increased risk of childhood leukaemia. However, the role of participation bias should not be discounted.

Adolescent↗

PubMed1993

Clinical evaluation of immunotherapy in early pregnancy with x-irradiated paternal mononuclear cells for primary recurrent aborters.

OBJECTIVE: The purpose of this study was to evaluate the beneficial effect of immunotherapy for the treatment of recurrent abortion. STUDY DESIGN: We immunized 106 primary recurrent aborters, twice at around 5 and 7 weeks of gestation, with intradermal injection of approximately 100 to 200 million x-irradiated (50 Gy) paternal mononuclear cells. We injected another 38 primary recurrent aborters in the same manner with only 1 million such paternal cells, to examine the relationship between the paternal cell dose used for immunization and pregnancy outcome. RESULTS: The pregnancy success rate (83.0%) in patients immunized with a large number of cells was significantly higher than that (55.3%) in those immunized with a small number of cells (p < 0.001). Furthermore, the frequency of twins in the former group was high (5.7%, five of 88). CONCLUSION: This positive relationship between the paternal cell dose used for immunization in early pregnancy and the pregnancy outcome reflects the efficacy of this mode of immunotherapy for recurrent aborters.

Abortion, Habitual↗

PubMed1984

Behavioral and neurochemical alterations in the offspring of rats after maternal or paternal inhalation exposure to the industrial solvent 2-methoxyethanol.

The industrial solvent 2-methoxyethanol (2ME) has antifertility effects in male rats at 300 ppm and is teratogenic in rats and rabbits at 50 ppm. The present research investigated if exposure of paternal or maternal animals to 25 ppm 2ME, the current U.S. permissible occupational exposure limit, would produce detectable effects in the offspring. Eighteen male young-adult Sprague-Dawley rats were exposed to 25 ppm 2ME 7 hr/day, 7 days/week for 6 weeks; they were then mated with untreated females which were allowed to deliver and rear their young. In addition, groups of 15 pregnant rats were exposed 7 hr/day on gestation days 7-13 or 14-20 and allowed to deliver and rear their young. At birth, litters were culled to 4 females and 4 males for behavioral testing of neuromotor function, activity, and simple learning ability on days 10 through 90. In addition, brains from newborn and 21-day-old offspring were analyzed for neurochemical deviations from controls. No effects on paternal or maternal animals, nor on the number or weight of live offspring, were noted. Behavioral testing revealed significant differences from controls only in avoidance conditioning of offspring of mothers exposed on days 7-13. In contrast, neurochemical deviations were observed in brains from 21-day-old offspring from the paternally exposed group as well as from both maternally exposed groups; changes were numerous in the brainstem and cerebrum but were fewer in the cerebellum and midbrain. Thus it appears that both paternal and maternal inhalation of 25 ppm 2ME produces some effect which is reflected in neurochemical deviations in the offspring.

Acetylcholine↗

PubMed1994

Women as mothers and wives in paternally incestuous families: coping with role conflict.

Although role conflict is well recognized for women in general, it has not been explored for women who are mothers and wives in paternally incestuous families. This study sought to remedy that oversight by analyzing the data gleaned from in-depth life history interviews with 20 women from paternally incestuous families who were just entering treatment. The women reported a moderate degree of conflict between their roles as mother and wife. Their strategies for coping with that conflict varied. Each described strategy was categorized according to the level of the role process at which it intervened, and was also evaluated in terms of its efficacy and its empowerment. The level of the coping strategy was somewhat, although not significantly, related to the duration of the paternal incest, and significantly related to its severity. The implications of these findings for the allegation of collusion made against women is discussed, and suggestions for therapeutic intervention with women from paternally incestuous families are presented.

Adaptation, Psychological↗

PubMed1988

Immunological studies in recurrent spontaneous abortion: effects of immunization of women with paternal mononuclear cells on lymphocytotoxic and mixed lymphocyte reaction blocking antibodies and correlation with sharing of HLA and pregnancy outcome.

The occurrence of maternal antipaternal lymphocytotoxic antibody (LCTA), mixed lymphocyte reaction blocking factors (MLRBF) and human leukocyte antigen (HLA) antigen sharing was studied in 115 couples with unexplained repeated spontaneous abortions (RSA). Comparisons were made to the same studies done on 41 couples with explained repeated miscarriages. We found no significant difference between the patient and control group with respect to the percent of couples sharing none, one, or two or more HLA-A,-B, or -DR antigens. Examination of the occurrence of LCTA and MLRBF likewise did not reveal differences between the groups, nor did the occurrence of these antibodies on initial testing correlate with HLA disparity between couples. Women with three or more spontaneous abortions were immunized with paternal mononuclear cells (MNC) if they met at least two of the following three criteria: they shared two or more HLA antigens; their serum was negative for paternal MNC-directed LCTA; their serum did not contain maternal versus paternal MLR blocking factors. Complete HLA, LCTA and MLRBF data pre- and post-treatment are available on 60 women. Sixty-three percent of women converted to LCTA positive 6 +/- 1 weeks after immunization, and 35% of women converted from negative to positive for MLR blocking after immunization. Fifty-eight women who had all three tests done prior to immunization became pregnant after immunization. Only 50% of this selected group have experienced successful pregnancy as judged by delivery of a live-born infant. In the patients presented, successful pregnancy outcome did not correlate with HLA antigen disparity, but successful patients were more likely than aborters to have either LCTA or MLRBF prior to pregnancy (28 vs. 7%). Post-immunization conversion to LCTA positive was more prevalent in the women who aborted after immunization (74%) compared to those who had successful pregnancy (48%) while MLR blocking antibody conversion from negative to positive was the same in both groups. The data indicate that neither HLA antigen sharing nor conversion to LCTA or MLR blocking positive after paternal WBC immunization are predictors for successful pregnancy outcome. Results so far suggest that conversion to LCTA positive after immunization may have a negative influence on pregnancy outcome.

Abortion, Habitual↗

PubMed1993

West Nile virus infection induces susceptibility of in vitro outgrown murine blastocysts to specific lysis by paternally directed allo-immune and virus-immune cytotoxic T cells.

Day 3 post-coitum BALB/c and (BALB/c x CBA/H)F1 blastocysts were isolated and hatched in replicate wells. Some were treated with interferon-gamma (IFN-gamma). Whilst others were infected with West Nile Virus (WNV) at 100 plaque-forming units per cell, for 18 h. Controls were mock-treated. Gamma-irradiated (2000 rads) CBA/H, (paternal) WNV-specific and allo(CBA/H)-specific cytotoxic T (Tc) cells were then added to replicates of infected, mock-infected or IFN-gamma-treated cultures for 20 h. [3H]Thymidine was then added for a further 8 h. [3H]Thymidine incorporation was inhibited by 40-50% in WNV-infected cultures exposed to WNV-paternal-specific Tc cells and by 30-40% in WNV-infected cultures exposed to allo-paternal-specific Tc cells compared to similarly exposed, uninfected, or unexposed, WNV-infected, or unexposed, uninfected cultures. No significant differences in [3H]thymidine incorporation were found between these controls and IFN-gamma-treated cultures exposed to allo-paternal-specific Tc cells or IFN-gamma-treated cultures not exposed to Tc cells. Parallel exposure of L929 fibroblasts to the same Tc cells irradiated with 500-8000 rads in doubling doses, showed that irradiation did not alter the efficacy or specificity of the Tc cells. Relevance to maternal anti-viral immune responses during implantation is discussed.

Animals↗

PubMed2006

Paternity leave in Sweden: costs, savings and health gains.

OBJECTIVES: The initial objective is to examine the relationship between paternity leave in 1978-1979 and male mortality during 1981-2001, and the second objective is to calculate the cost-effectiveness of the 1974 parental insurance reform in Sweden. METHODS: Based on a population of all Swedish couples who had their first child together in 1978 (45,801 males), the risk of death for men who took paternity leave, compared with men who did not, was estimated by odds ratios. The cost-effectiveness analysis considered costs for information, administration and production losses, minus savings due to decreased sickness leave and inpatient care, compared to health gains in life-years and quality-adjusted life-years (QALYs). RESULTS: It is demonstrated that fathers who took paternity leave have a statistically significant decreased death risk of 16%. Costs minus savings (discounted values) stretch from a net cost of EUR 19 million to a net saving of EUR 11 million, and the base case cost-effectiveness is EUR 8000 per QALY. CONCLUSIONS: The study indicates that that the right to paternity leave is a desirable reform based on commonly stated public health, economic, and feminist goals. The critical issue in future research should be to examine impact from health-related selection.

Cost-Benefit Analysis↗

PubMed2005

Epigenetic abnormalities of the mouse paternal zygotic genome associated with microinsemination of round spermatids.

Although round spermatid injection can be used to create progeny for males who do not produce mature sperm, the rate of successful embryogenesis after such procedures is significantly lower than that for similar procedures using mature spermatozoa. The mechanisms underlying this difference are unknown. In this study, we demonstrate that, unlike the normal paternal genome, the paternal zygotic genome derived from a round spermatid is highly remethylated before first mitosis after demethylation. Genomes from elongated spermatids exhibited an intermediate level of DNA methylation, between those of round spermatids and mature spermatozoa, suggesting that the male germ cell acquires the ability to maintain its undermethylated state in the paternal zygotic genome during this phase of spermiogenesis. In addition, treatment of zygotes with trichostatin A led to a significant reduction in DNA methylation, specifically in the spermatid-derived paternal genome, except for the pericentromeric regions enriched by trimethylation of Lys9 of histone H3. These data provide insight into epigenetic errors that may be associated with the poor development of embryos generated from immature spermatozoa.

Animals↗

PubMed2006

Assessment of serum follicle-stimulating hormone level and testicular volume for prediction of paternity potential in pubertal boys who underwent bilateral orchiopexy in childhood.

PURPOSE: We examined infertile adults for the presence of spermatozoa in the testes, serum FSH level and testicular volume to predict paternity potential in pubertal boys who had undergone bilateral orchiopexy in childhood. MATERIALS AND METHODS: The study included 58 idiopathic infertile men (group 1), 14 infertile men who had undergone bilateral orchiopexy in childhood (group 2) and 21 pubertal boys who had undergone bilateral orchiopexy in childhood (group 3). We evaluated the correlation between FSH level and testicular volume in all groups. In groups 1 and 2 the testes were examined for the presence of spermatozoa using bilateral testicular biopsy samples. RESULTS: Judging from the presence of spermatozoa in the testes and correlation between FSH level and testicular volume, 14 patients in group 1 (24%) were categorized as being at high risk, 32 (55%) at intermediate risk and 12 (21%) at low risk for loss of paternity potential, with spermatozoa positive rates of 0%, 49% and 100%, respectively. In comparison, 4 patients in group 2 (29%) were categorized as being at high risk, 7 (50%) at intermediate risk and 3 (21%) at low risk, with spermatozoa positive rates of 0%, 43% and 100%, respectively. According to this categorization, 19% of pubertal boys in group 3 were at high risk and may already have lost their paternity potential. CONCLUSIONS: Despite bilateral orchiopexy in childhood, some male adolescents may not have the potential for paternity.

Adolescent↗

PubMed1998

Paternal alcohol exposure: developmental and behavioral effects on the offspring of rats.

The effect of paternal alcohol exposure on neurochemical and behavioral parameters was investigated using as a model system glial cells derived from newborn rat brain and cultured for 4 weeks. The total brain neurochemical parameters from rats born to mothers sired by an alcohol treated father were also investigated. Enzymatic markers of nerve cell development (enolase isoenzymes and glutamine synthetase) and the defense system (superoxide dismutase) against free radicals formed during alcohol degradation were measured in order to evaluate nerve cell damage. Behavioral locomotor tests (open-field, novelty-seeking, light/dark) were carried out to show long-lasting effects of paternal alcoholization on the offspring. Behavioral and developmental alterations were found until 1 year of age in the offspring and a significant growth retardation was observed in the males. Our results suggest that paternal alcohol exposure produces developmental and behavioral effects in the offspring. The consequence of either alcohol withdrawal during stage one spermatogenesis, or maternal diet supplementation with manganese during pregnancy were investigated. It was observed that some of the effects of paternal alcohol exposure on the offspring may be reversed by these treatments.

Animals↗

PubMed2000

Evaluating the parent-of-origin effect in bipolar affective disorder. Is a more penetrant subtype transmitted paternally?

BACKGROUND: Numerous genetic mechanisms and modes of transmission underlying bipolar affective disorder (BPAD) have been postulated. Recently, the discovery of genomic imprinting and mitochondrial transmission of illness in humans has stimulated study of parent-of-origin effects in the transmission of BPAD. METHODS: We examined a large sample of families from an associated linkage study to search for a possible parent-of-origin effect. Selecting for unilineal families with at least one offspring and/or parent diagnosed with BPAD after structured interview, we conducted three analyses: (1) the rates of illness among mothers and fathers of offspring affected with BPAD; (2) the observed frequency of transmission and rates of illness among maternal and paternal lineages; and (3) the rates of affective illness among offspring of parents affected with BPAD. RESULTS: Our results indicate no significant differences in the rates of illness among mothers and fathers of offspring affected with BPAD. Also, the frequency of transmission and rates of illness among maternal and paternal lineages did not differ significantly. However, the rate of BPAD among the offspring of fathers affected with BPAD was significantly higher than for mothers with the illness. LIMITATIONS: Substantially more women than men, and maternal than paternal relatives were studied - introducing possible gender biases. CONCLUSIONS: These results suggest a possible paternal parent-of-origin effect.

Bipolar Disorder↗

PubMed2000

Sibling incest and formulation of paternity probability: case report.

Paternity determination of a fetus whose mother was admitted to an institution for the welfare and health of handicapped persons was requested of us by a doctor and lawyer of the institution. The fetus was recovered by a legal artificial abortion based on the Act on Maternity Health and Welfare (Japan) with the permission of the custodian. Commercially available MCT118, HLADQA, PM, and 9 STRs were tested for DNA samples from the fetus, the mother, her younger brother, her father, her grandfather, and 4 staff members of the institution. Only the brother was not excluded and the paternity probability was estimated at 99.857% on the basis of newly formulated expressions for multiallelic loci on the assumption of sibling incest. We concluded then that the fetus was fathered by the brother. DNA fingerprinting with multilocus and single locus minisatellite probes which were performed to confirm the paternity also support the conclusion. Bandsharing frequencies between the family members, however, did not necessarily reflect their actual kinship, which findings suggest that multilocus DNA fingerprinting requires further accumulation of data for consanguineous cases such as incest. Universal formulation for calculating paternity probability for a sibling incest case on the basis of multiallelic monolocus polymorphisms is also presented.

Journal Article↗

PubMed2001

Maternal versus paternal expression of a LacZ transgene in preimplantation mouse embryos: effects of genetic background and 2-cell block.

The expression of a transgene NI-ROSA LacZ (LacZtg) trapped into the genes for two presumably untranslated, ubiquitously expressed RNAs, was studied in preimplantation mouse embryos with respect to penetrance (fraction of expressing embryos) and to localisation of beta-galactosidase activity. With maternal origin in NMRI mice beta-galactosidase was first detected within one dot in the cytoplasm of zygotes at 30 h post-hCG. The staining pattern progressed to small clusters and to dense, homogeneous staining of the entire cytoplasm during further development. Within the NMRI background, penetrance in utero was delayed by at least 6 h when the transgene was of paternal as compared with maternal origin. Paternal transgene expression increased marginally during culture to 50 h after explantation of embryos at 30-48 h post-hCG and remained low or decreased in the '2-cell block'. Expression of a paternal transgene in preimplantation embryos developing in utero was further delayed in the maternal MF1 as compared with the NMRI background. In contrast to NMRI x NMRI embryos with paternally derived transgene, expression increased with time during the 2-cell block in MF1 x NMRI embryos. Thus, in the earliest phase of mammalian development expression of this LacZtg is influenced by parental origin, maternal genetic background and environment. The spatial distribution of the gene product is developmentally controlled.

Animals↗

PubMed2002

Maternal depression, paternal psychopathology, and adolescent diagnostic outcomes.

The authors examined the relationship between maternal depression, paternal psychopathology, and adolescent diagnostic outcomes in a community sample of 522 Australian families. They also examined whether chronic family stress, father's expressed emotion, and parents' marital satisfaction mediated the relationship between parental psychopathology and adolescent outcomes. Mother's education, child's gender, and family income were covaried in all analyses. Results revealed that maternal depression and paternal depression had an additive effect on youth externalizing disorders. In addition, maternal depression interacted with both paternal depression and paternal substance abuse in predicting youth depression but not youth nondepressive disorders. Chronic family stress and father's expressed emotion appeared to mediate the relationship between parental psychopathology and youth depression.

Adolescent↗

PubMed2000

Evolution and proximate expression of human paternal investment.

In more than 95% of mammalian species, males provide little direct investment in the well-being of their offspring. Humans are one notable exception to this pattern and, to date, the factors that contributed to the evolution and the proximate expression of human paternal care are unexplained (T. H. Clutton-Brock, 1989). The nature, extent, and influence of human paternal investment on the physical and social well-being of children are reviewed in light of the social and ecological factors that are associated with paternal investment in other species. On the basis of this review, discussion of the evolution and proximate expression of human paternal investment is provided.

Adult↗

PubMed1989

Preferential germline mutation of the paternal allele in retinoblastoma.

The event triggering malignant proliferation in 70% of retinoblastoma tumours is loss of heterozygosity for chromosome 13q14, whereby the normal retinoblastoma gene (RB1) allele is lost and an already mutated RB1 allele remains in the tumour. The first allele suffers a mutational event--deletion, duplication or point mutation (manuscript in preparation)--either in the germ line (all bilateral patients) or in a somatic retinal cell (most unilateral patients). Most bilateral patients have no family history of retinoblastoma and are presumed to have new germline mutations which arose in the egg, sperm or early embryo. We have determined the parental origin of the retained allele in nine retinoblastoma tumours from eight unrelated non-familial cases by using RB1-linked genetic markers. Six tumours retained the paternal allele and three retained the maternal allele. Of the three unilateral tumours, only one retained the paternal RB1 allele. Thus, there is no evidence that the paternal RB1 allele is preferentially retained in retinoblastoma, as has been suggested to be the case in osteosarcoma. By contrast, tumours from four of the five bilateral patients retained the paternal RB1 allele. This suggests either that new germline RB1 mutations arise more frequently during spermatogenesis than during oogenesis, or that imprinting in the early embryo affects chromosomal susceptibility to mutation.

Alleles↗

PubMed1990

Paternal origin of new mutations in von Recklinghausen neurofibromatosis.

Von Recklinghausen neurofibromatosis (NF-1) is a common autosomal dominant disorder. The estimated new mutation rate (1 x 10(-4] is one of the highest for a human disorder. Here we report that in 12 of 14 families we have analysed, the new mutation is of paternal origin. This result is similar to that recently obtained for retinoblastoma. In other genetic disorders that show a bias towards paternal origin of new mutations, there is a marked increase in the incidence of mutations with paternal age, consistent with the mutations arising from replication errors in mitosis of spermatogonial stem cells. In retinoblastoma and NF-1, however, such paternal age effects are slight or absent. The mechanism or timing of germline mutation could therefore be different in the two cases.

Adult↗