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PubMed2004

Paternal alcohol dependence and offspring suicidal behaviors in a children-of-twins study.

INTRODUCTION: In substance abusing families, sources of familial comorbidity are potentially confounded by genetic-environmental (GE) interplays. The children-of-twins (COT) design can be used to elucidate the association of a parental trait and an offspring outcome such as the association of parental alcoholism and offspring suicidality. METHODS: We examined the association of paternal alcoholism and offspring suicidal behaviors in an adolescent and young adult COT sample of 'Vietnam Era Twins' offspring who had completed an interview including a comprehensive assessment of lifetime suicidal behaviors. We stratified the COT sample into four groups contingent upon paternal zygosity, MZ versus DZ, and lifetime paternal alcohol dependence history (AD), positive versus negative. We examined whether the relationship of paternal alcoholism and offspring suicidality was best explained by genetic predispositions common to alcoholism and suicidality or by GE interplay--environmental influences correlated with parental alcoholism or the interaction of genetic and environmental factors. RESULTS: Our results suggest a main effect of paternal alcoholism on offspring suicide attempt; COT analyses do not support a purely genetic explanation for this association. DISCUSSION: Suicide attempts probably result from GE interplays and must be studied in genetically informative samples of offspring of substance abusing parents.

Adolescent↗
PubMed2004

No evidence for paternal inheritance of mtDNA in patients with sporadic mtDNA mutations.

With the publication of a patient with severe exercise intolerance, in whom the mutated mtDNA in muscle was shown to be paternally inherited, the strict maternal inheritance of mtDNA was challenged. Paternal mtDNA inheritance may have gone unrecognized in cases of mitochondrial disease with no clear maternal pattern of inheritance because mitochondrial haplotypes are rarely investigated in diagnostic analyses. To find further evidence for a paternal inheritance of mtDNA, we reinvestigated 12 patients with mitochondrial myopathy, in whom the pathogenic mutation was known to be sporadic. We compared the mtDNA haplotypes from the patient's muscle with that of the mtDNA haplotypes in blood from either the mother or the patient. No evidence of paternal inheritance of mtDNA was found in this small study. Although these findings indicate that the paternal inheritance of mtDNA is rare, they do not rule out that the phenomenon may occur at a rate that could still affect genetic counselling and anthropological research.

DNA, Mitochondrial↗
PubMed1999

Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus.

Two patients who presented at birth with neonatal diabetes mellitus (NDM) are described: one with paternal uniparental disomy for chromosome 6 and one with normal, biparental inheritance. The first child presented with low birth weight, macroglossia, hypertelorism, and club foot in addition to NDM. In this patient hyperglycemia was transient, and insulin treatment was discontinued at 4 months of age. The second child also presented with low birth weight but was normal in appearance, and insulin dependence continues after 5 years. Genetic analysis with polymorphic DNA markers for chromosome 6 indicated the presence of paternal uniparental disomy (UPD) in the first case and normal, biparental inheritance in the second case. Paternal UPD 6 has been reported in 8 previous cases of which 6 showed NDM. Three cases with paternal UPD 6 also included additional anomalies, such as macroglossia, not usually associated with NDM. Therefore the simultaneous finding of NDM and macroglossia should be a strong indicator for genetic testing. The genetic finding of paternal UPD 6 allows prediction of a transient, rather than permanent, form of diabetes mellitus and no increased recurrence risk of transient NDM in subsequent pregnancies.

Aneuploidy↗
PubMed2003

Men who kill their own children: paternal filicide incidents in contemporary Fiji.

OBJECTIVE: Filicide, or parental murder of offspring, constitutes a major portion of lethal violence perpetrated against children worldwide. Despite the global nature of the phenomenon, researchers have focused their studies on the developed industrialized societies with the consequent neglect of small, developing societies. Second, there is a paucity of empirical data on child homicide committed by fathers. This study therefore explores the nature and extent of paternal filicides in Fiji, a non-Western society, and the social and cultural forces underlying them in order to enhance our knowledge of the phenomenon. METHOD: Information was obtained from a number of sources, including (a) a police homicide logbook, (b) newspaper reports of homicide, and (c) detailed interviews conducted with criminal justice and medical personnel. Information from these data sources were consolidated to construct case histories of paternal filicides. These cases were then analyzed for dominant themes. Case illustrations are presented in the text. RESULTS: Several of the study's findings are congruent with other studies of paternal filicides: poor, working class fathers were the offenders in all cases. As a corollary, their victims were from low socioeconomic backgrounds. Regarding location, paternal filicides occurred in the home of the offender and victim. The filicides were the culmination of stresses and strains associated with marital disharmony and excessive corporal child-control strategies. CONCLUSIONS: The general conclusion of this study is that further research in non-Western societies has the potential to increase our understanding of the social factors and processes involved in paternal child murders. We will then be better positioned to craft effective intervention strategies.

Adult↗
PubMed2002

Kinetics of the pregnancy-induced humoral and cellular immune response against the paternal HLA class I antigens of the child.

Pregnancy can prime the maternal humoral immune response against paternal human leukocyte antigens (HLA) of the child. Previous studies have reported that formation of antibodies against inherited paternal HLA is associated with the presence of primed cytotoxic T lymphocytes (CTLs) specific for these antigens. Recently, we reported that primed CTLs can persist for more than 10 years after pregnancy even if the antibodies have disappeared. In the present study we studied the kinetics of the pregnancy induced immune response of the T-cell and B-cell compartment. In 12 women, who had specific antibodies against the paternal HLA antigens of the child (child mismatch) at the time of delivery, we analyzed the CTLp frequencies against the paternal HLA antigens from the time of delivery up to 2 years after. The contribution of primed CTLs to these CTLp frequencies was tested by limiting dilution analysis in the absence and presence of monoclonal antibodies specific for CD8. In contrast to naïve CTLs, primed CTLs are resistant to CD8 antibodies. Disappearance of the antibodies was not associated with a decrease of the number of CTLp directed against the paternal antigens, towards which the antibodies were originally directed. However, in women where the antibodies disappeared, a decrease of primed child mismatch specific CTLs was found, whereas in women where the antibodies persist, the population of primed CTLs remained stable up to 2 years after delivery. Our data suggest a functional correlation between the T-cell and B-cell allorepertoire. Although the kinetics do not run completely in parallel, disappearance of the anti-HLA antibodies in the first 2 years after delivery is related with a decrease of primed child mismatch specific CTLs. These data may be relevant for transplantation of female recipients with historical, pregnancy-induced HLA alloantibodies.

Antibody Affinity↗
PubMed2007

Paternal smoking is associated with increased risk of child malnutrition among poor urban families in Indonesia.

OBJECTIVE: Paternal smoking is highly prevalent in Asia, and tobacco may account for a large proportion of household expenditures among poor families. We sought to characterise the relationship between paternal smoking, child malnutrition and food expenditures. DESIGN: Data on smoking, household expenditures and child malnutrition were examined in a stratified multistage cluster sample of households in the Indonesia nutrition surveillance system. Main outcome measures were child wasting (weight-for-height Z-score < - 2), underweight (weight-for-age Z-score < - 2) and stunting (height-for-age Z-score < - 2), and severe wasting, underweight and stunting (defined by respective Z-scores < - 3). SETTING: In total, 175,583 households from urban slum areas in Indonesia. SUBJECTS: Children 0-59 months of age. RESULTS: The prevalence of paternal smoking was 73.8%. After adjusting for child gender and age, maternal age and education, and weekly per capita household expenditures, paternal smoking was associated with child stunting (odds ratio (OR) = 1.11, 95% confidence interval (CI) 1.08-1.14, P < 0.0001), severe wasting (OR = 1.17, 95% CI 1.03-1.33, P = 0.018) and severe stunting (OR = 1.09, 95% CI 1.04-1.15, P < 0.001). In households where the father was a smoker, tobacco accounted for 22% of weekly per capita household expenditures, with less money spent on food compared with households in which the father was a non-smoker. CONCLUSIONS: Among poor families in urban slum areas of Indonesia, paternal smoking diverts household money from food to tobacco and exacerbates child malnutrition.

Adult↗
PubMed1990

Relationship of personal-social variables to belief in paternalism in parent caregiving situations.

Paternalism in family caregiving may jeopardize the older persons' autonomy; it needs to be better understood. Study objectives were to determine the relationship of belief in paternalism to personal-social characteristics and to determine the relative importance of these variables as predictors of belief in paternalism. Forty-six pairs of daughters (age 49.7) and mothers (age 77.7) were measured on belief in paternalism, dogmatism, attitude toward elders, affective feelings toward the other, and background and caregiving variables. Among both mothers and daughters, dogmatism and attitude toward elders were related to belief in paternalism; daughters' affective feelings was also related. Caregiving variables were unrelated, and demographic background was important only for daughters. Attitude toward elders was the strongest predictor. Results were interpreted in terms of a traditional family ideology.

Adult↗
PubMedDate not supplied

An extrachromosomal factor causing loss of paternal chromosomes.

Extrachromosomal inheritance is ubiquitous among plants and animals; however, most extrachromosomal factors are uniparentally inherited through females, but not through males. Examples include chloroplasts, mitochondria and a variety of intracellular symbionts. The only known exception to maternal extrachromosomal inheritance in an animal is a paternally transmitted sex ratio factor (psr) which causes all-male families in the parasitic wasp, Nasonia vitripennis. Normally in this wasp, male offspring are haploid and develop from unfertilized eggs whereas females are diploid and develop from fertilized eggs. The psr factor is either a venereally transmitted infection which prevents egg fertilization (and therefore causes all-male families), or a factor transmitted to eggs by the sperm of males carrying psr, which somehow prevents incorporation of the paternal chromosomes. Here we report that sperm from psr males fertilizes eggs, but that the paternal chromosomes are subsequently condensed into a chromatin mass before the first mitotic division of the egg and do not participate in further divisions. Resulting haploid offspring are male, but have inherited the paternal factor. This extrachromosomal factor promotes its own transmission at the expense of the paternal chromosomes, and therefore can be considered a 'selfish' genetic element.

Animals↗
PubMed2000

Delayed activation of the paternal genome during seed development.

Little is known about the timing of the maternal-to-zygotic transition during seed development in flowering plants. Because plant embryos can develop from somatic cells or microspores, maternal contributions are not considered to be crucial in early embryogensis. Early-acting embryo-lethal mutants in Arabidopsis, including emb30/gnom which affects the first zygotic division, have fuelled the perception that both maternal and paternal genomes are active immediately after fertilization. Here we show that none of the paternally inherited alleles of 20 loci that we tested is expressed during early seed development in Arabidopsis. For genes that are expressed at later stages, the paternally inherited allele becomes active three to four days after fertilization. The genes that we tested are involved in various processes and distributed throughout the genome, indicating that most, if not all, of the paternal genome may be initially silenced. Our findings are corroborated by genetic studies showing that emb30/gnom has a maternal-effect phenotype that is paternally rescuable in addition to its zygotic lethality. Thus, contrary to previous interpretations, early embryo and endosperm development are mainly under maternal control.

Alleles↗
PubMed2000

De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch.

Prader-Willi syndrome (PWS) is a neurogenetic disease characterized by infantile hypotonia, gonadal hypoplasia, obsessive behaviour and neonatal feeding difficulties followed by hyperphagia, leading to profound obesity. PWS is due to a lack of paternal genetic information at 15q11-q13 (ref. 2). Five imprinted, paternally expressed genes map to the PWS region, MKRN3 (ref. 3), NDN (ref. 4), NDNL1 (ref. 5), SNRPN (refs 6-8 ) and IPW (ref. 9), as well as two poorly characterized framents designated PAR-1 and PAR-5 (ref. 10). Imprinting of this region involves a bipartite 'imprinting centre' (IC), which overlaps SNRPN (refs 10,11). Deletion of the SNRPN promoter/exon 1 region (the PWS IC element) appears to impair the establishment of the paternal imprint in the male germ line and leads to PWS. Here we report a PWS family in which the father is mosaic for an IC deletion on his paternal chromosome. The deletion chromosome has acquired a maternal methylation imprint in his somatic cells. We have made identical findings in chimaeric mice generated from two independent embryonic stem (ES) cell lines harbouring a similar deletion. Our studies demonstrate that the PWS IC element is not only required for the establishment of the paternal imprint, but also for its postzygotic maintenance.

Adult↗
PubMed2004

Mapping of paternal-sex-ratio deletion chromosomes localizes multiple regions involved in expression and transmission.

The paternal-sex-ratio (PSR) chromosome in the parasitic wasp Nasonia vitripennis is a submetacentric supernumerary (B chromosome). Males transmit PSR, but after fertilization it causes the loss of the paternal autosomes. Paternal genome loss caused by PSR results in the conversion of a female (diploid) zygote into a male (haploid) under haplodiploid sex determination. In this study, site-specific markers were developed to assay deletion derivatives of PSR. Both polymerase chain reaction and Southern hybridization were used to detect the presence/absence of 16 single-site markers on a set of 20 functional and nine nonfunctional deletion chromosomes. Based on the pattern of marker loss on the deletion chromosomes, the basic organization of PSR was revealed. Two sets of markers were deleted independently, apparently representing the two arms of the submetacentric chromosome. The presence or absence of specific regions was examined in relation to phenotypic characteristics of the deletion chromosomes; ability to cause paternal genome loss, and stability in mitotic cell divisions. Rather than identifying a single region on PSR as being responsible for PSR function, the results suggest that the retention of one of two chromosomal regions is sufficient for causing paternal genome loss. Furthermore, a region was identified that is tightly correlated with mitotic stability, as measured from chromosomal transmission rates. Functional chromosomes with short-arm deletions had high (approximately 100%) transmission rates, whereas functional chromosomes with long-arm deletions had low (approximately 85%) transmission rates.

Animals↗
PubMed2002

Molecular determination of paternity in a natural population of the multiply mating polygynous lizard Eulamprus heatwolei.

We studied the mating system of the southern water skink, Eulamprus heatwolei, during spring and summer (encompassing the breeding season) in a population in southeastern Australia. We examined potential attributes that might influence the mating system and male reproductive success including home range size, physical proximity of adults and body size, and then genotyped all mothers, offspring and potential sires. Home range overlap of both sexes was extensive, with adult females sharing the greatest amount of space with each other and adult males the least amount of space with each other. However, not all adults hold home ranges. We classified approximately one quarter of adult males as home range holders and the rest as 'floaters'. Adult females occupy home ranges more than males, with approximately three-quarters classified as home range holders. Home range ownership is not correlated with body size for either sex, however, male body size is positively correlated with the number of adult female home ranges that his home range overlaps and adult male home ranges are larger than those of females. We used microsatellite genotyping to assign paternities to 55 offspring from 17 litters and then compared this data with our home range and behavioural observations. This species displays extreme levels of multiple paternity given the small mean clutch size of three. Multiple paternity was confirmed in 11 (64.7%) of 17 clutches but three other clutches (for a total of 82.4%) also may display multiple paternity. A total of 30 offspring from 12 litters were assigned to 10 of the 32 genotyped adult males from our study site. Of these 10 adult males, half were home range holders. Five complete clutches and a total of 25 out of the 55 offspring could not be positively assigned to any male surveyed as part of the study and were attributed to floater males or resident males adjacent to our study site that had not been genotyped. While sample sizes are small, neither male home range ownership nor body size is significantly correlated with the number of paternities a male obtained. Our study suggests a polygynous mating system for this species.

Animals↗
PubMed2000

Tracking paternal genes with DALP markers in a pseudoarrhenotokous reproductive system: biparental transmission but haplodiploid-like inheritance in the mite Neoseiulus californicus.

The complexity of some sexual reproductive systems in arthropods still leaves both their genetic and epigenetic determinism and their evolutionary significance poorly understood. Pseudoarrhenotoky is characterized by obligate fertilization and differential inactivation and/or elimination of paternal chromosomes in embryos that develop into males. Here, we investigate how the paternal genome is transmitted in a pseudoarrhenotokous mite, Neoseiulus californicus, using codominant genetic markers detected by DALP (direct amplification of length polymorphism). Transmission patterns of parental alleles through one and two generations are reported at four or five loci corresponding to four linkage groups. Our data provide strong evidence for selective elimination of the paternal genome among male tissues. Sperm contained maternal genes exclusively, whereas some male somatic tissues retained most if not all paternal chromosomes. No recombination between parental genomes prior to paternal genome elimination from the embryonic germ line was observed. These data allow a reinterpretation of previous phenotypic and cytogenetic observations in these mites, from which we suggest some relevant mechanistic and evolutionary implications. In addition, this is the first published study using polymorphic codominant loci detected by the recently developed DALP method.

Animals↗
PubMed1998

Statistical confidence for likelihood-based paternity inference in natural populations.

Paternity inference using highly polymorphic codominant markers is becoming common in the study of natural populations. However, multiple males are often found to be genetically compatible with each offspring tested, even when the probability of excluding an unrelated male is high. While various methods exist for evaluating the likelihood of paternity of each nonexcluded male, interpreting these likelihoods has hitherto been difficult, and no method takes account of the incomplete sampling and error-prone genetic data typical of large-scale studies of natural systems. We derive likelihood ratios for paternity inference with codominant markers taking account of typing error, and define a statistic delta for resolving paternity. Using allele frequencies from the study population in question, a simulation program generates criteria for delta that permit assignment of paternity to the most likely male with a known level of statistical confidence. The simulation takes account of the number of candidate males, the proportion of males that are sampled and gaps and errors in genetic data. We explore the potentially confounding effect of relatives and show that the method is robust to their presence under commonly encountered conditions. The method is demonstrated using genetic data from the intensively studied red deer (Cervus elaphus) population on the island of Rum, Scotland. The Windows-based computer program, CERVUS, described in this study is available from the authors. CERVUS can be used to calculate allele frequencies, run simulations and perform parentage analysis using data from all types of codominant markers.

Animals↗
PubMed2001

Paternity and relatedness in wild chimpanzee communities.

The genetic structure of three contiguous wild chimpanzee communities in West Africa was examined to determine the extent to which the community, the mixed-sex social unit of chimpanzees, represents a closed reproductive unit. An analysis of paternity for 41 offspring resulted in 34 cases of paternity assignment to an adult male belonging to the same community. Among the 14 offspring for which all potential within-community fathers have been tested, one likely case of extra-group paternity (EGP) has been identified, suggesting an incidence of EGP of 7%. This more extensive analysis contradicts a previous genetic study of the Tai chimpanzees that inferred 50% extra-group fathers. We suggest, based on direct comparison of results for 33 individuals at 1 microsatellite locus and direct comparison of paternity assignments for 11 offspring, that the error rate in the previous study was too high to produce accurate genotypes and assignments of paternity and hence caused the false inference of a high rate of EGP. Thus, the community is the primary but not exclusive unit for reproduction in wild chimpanzees, and females do not typically reproduce with outside males. Despite the inferred low level of gene flow from extra-community males, relatedness levels among the community males are not significantly higher than among community females, and the distribution of genetic relationships within the group suggests that, rather than a primarily male-bonded social structure, the group is bonded through relationships between males and females. Kinship may explain cooperative behaviors directed against other communities, but is unlikely to explain the high levels of affiliation and cooperation seen for male within-community interactions.

Animals↗
PubMed1998

Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins.

The GNAS1 gene encodes the alpha subunit of the guanine nucleotide-binding protein Gs, which couples signaling through peptide hormone receptors to cAMP generation. GNAS1 mutations underlie the hormone resistance syndrome pseudohypoparathyroidism type Ia (PHP-Ia), so the maternal inheritance displayed by PHP-Ia has raised suspicions that GNAS1 is imprinted. Despite this suggestion, in most tissues Gsalpha is biallelically encoded. In contrast, the large G protein XLalphas, also encoded by GNAS1, is paternally derived. Because the inheritance of PHP-Ia predicts the existence of maternally, rather than paternally, expressed transcripts, we have investigated the allelic origin of other mRNAs derived from GNAS1. We find this gene to be remarkable in the complexity of its allele-specific regulation. Two upstream promoters, each associated with a large coding exon, lie only 11 kb apart, yet show opposite patterns of allele-specific methylation and monoallelic transcription. The more 5' of these exons encodes the neuroendocrine secretory protein NESP55, which is expressed exclusively from the maternal allele. The NESP55 exon is 11 kb 5' to the paternally expressed XLalphas exon. The transcripts from these two promoters both splice onto GNAS1 exon 2, yet share no coding sequences. Despite their structural unrelatedness, the encoded proteins, of opposite allelic origin, both have been implicated in regulated secretion in neuroendocrine tissues. Remarkably, maternally (NESP55), paternally (XLalphas), and biallelically (Gsalpha) derived proteins all are produced by different patterns of promoter use and alternative splicing of GNAS1, a gene showing simultaneous imprinting in both the paternal and maternal directions.

Alleles↗
PubMed1991

Three cases of disputed paternity in dogs resolved by the use of DNA fingerprinting.

DNA fingerprinting with the probes 33.15 and alpha-globin 3'HVR has been used to resolve three cases of disputed paternity in dogs. For each pedigree it was necessary to establish which bands in the DNA fingerprints of the offspring were of paternal origin, and then establish which putative sire carried all these bands. In the first case, a litter of Rhodesian Ridgebacks, twelve DNA bands were informative in establishing paternity. In the second case, a litter of Afghan hounds, five DNA bands established paternity, Lastly, in a litter of Border collies, five DNA bands established paternity. In each case a single dog only sired the entire litter.

Journal Article↗
PubMed1998

Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis.

Molecular analysis of a patient affected by the autosomal recessive skeletal dysplasia, pycnodysostosis (cathepsin K deficiency; MIM 265800), revealed homozygosity for a novel missense mutation (A277V). Since the A277V mutation was carried by the patient's father but not by his mother, who had two normal cathepsin K alleles, paternal uniparental disomy was suspected. Karyotyping of the patient and of both parents was normal, and high-resolution cytogenetic analyses of chromosome 1, to which cathepsin K is mapped, revealed no abnormalities. Evaluation of polymorphic DNA markers spanning chromosome 1 demonstrated that the patient had inherited two paternal chromosome 1 homologues, whereas alleles for markers from other chromosomes were inherited in a Mendelian fashion. The patient was homoallelic for informative markers mapping near the chromosome 1 centromere, but he was heteroallelic for markers near both telomeres, establishing that the paternal uniparental disomy with partial isodisomy was caused by a meiosis II nondisjunction event. Phenotypically, the patient had normal birth height and weight, had normal psychomotor development at age 7 years, and had only the usual features of pycnodysostosis. This patient represents the first case of paternal uniparental disomy of chromosome 1 and provides conclusive evidence that paternally derived genes on human chromosome 1 are not imprinted.

Adult↗