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Fluorescence markers were studied in 40 patients with Down's syndrome and their parents. In 11 cases maternal and in 5 cases paternal non-disjunction could be shown. The disjunctional event occurred in the first meiotic division in 5 maternal and in 2 paternal cases. A second division failure was found in 4 maternal and 2 paternal cases. In 3 cases the failure could either be of first or second meiotic division origin.
Uniparental disomy (UPD) is defined as the presence of a chromosome pair that derives from only one parent in a diploid individual. The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA). We report here the second case of paternal UPD for chromosome 1 in a male patient with CIPA who developed normally at term and did not show overt dysmorphisms or malformations. He had only the usual features of CIPA with a homozygous mutation at the TRKA locus and a normal karyotype with no visible deletions or evidence of monosomy 1. Haplotype analysis of the TRKA locus and allelotype analyses of whole chromosome 1 revealed that the chromosome pair was exclusively derived from his father. Non-maternity was excluded by analyses of autosomes other than chromosome 1. Thus, we have identified a complete paternal isodisomy for chromosome 1 as the cause of reduction to homozygosity of the TRKA gene mutation, leading to CIPA. Our findings further support the idea that there are no paternally imprinted genes on chromosome 1 with a major effect on phenotype. UPD must be considered as a rare but possible cause of autosomal recessive disorders when conducting genetic testing.
Paternal nondisjunction accounts for approximately 5% of cases of trisomy 21. To test the hypothesis that, in some such cases, the fathers might be predisposed to meiotic nondisjunction, we utilized fluorescence in situ hybridization (FISH) to screen for aneuploidy in sperm. We analyzed sperm samples from ten males with a trisomy 21 offspring of paternal origin. Among these individuals, the overall frequency of disomy 21 was 0.15%, comparable to estimates of disomy 21 in the general male population. Furthermore, none of the ten fathers of trisomy 21 individuals had significantly elevated levels of disomic sperm. Thus, our results provide no evidence that the occurrence of a trisomy 21 conceptus of paternal origin imparts an increased risk of trisomy in subsequent pregnancies.
In this paper, the stages of normal sexual reproduction between pollen tube penetration of the archegonium and early embryo formation in Pinus tabulaeformis are described, emphasizing the transmission of parental cytoplasm, especially the DNA-containing organelles--plastids and mitochondria. The pollen tube growing in the nucellus contained an irregular tube nucleus followed by a pair of sperm cells. The tube cytoplasm contained abundant organelles, including starch-containing plastids and mitochondria. The two sperm cells differed in their volume of cytoplasm. The leading sperm, with more cytoplasm, contained abundant plastids and mitochondria, while the trailing one, with a thin layer of cytoplasm, had very few organelles. The mature egg cell contained a great number of mitochondria, whereas it lacked normal plastids. At fertilization, the pollen tube penetrated into the egg cell at the micropylar end and released all of its contents, including the two sperms. One of the sperm nuclei fused with the egg nucleus, whereas the other one was retained by the receptive vacuole. Very few plastids and mitochondria of male origin were observed around the fusing sperm and egg nuclei, while the retained sperm nucleus was surrounded by a large amount of male cytoplasm. The discharged tube cytoplasm occupied a large micropylar area in the egg cell. In the free nuclear proembryo, organelles of maternal and paternal origins intermingled in the neocytoplasm around the free nuclei. Most of the mitochondria had the same features as those of the egg cell, but some appeared to be from sperm cells and tube cytoplasm. Plastids were obviously of male origin, with an appearance similar to those of the sperm or tube cells. After cellularization of the proembryo, maternal mitochondria became more abundant than the paternal ones and the plastids enlarged and began to accumulate starch. The results reveal the cytological mechanism for paternal inheritance of plastids and biparental inheritance of mitochondria in Chinese pine.
To investigate the involvement of uniparental disomies (UPDs) in spontaneous abortion, the polymorphic patterns of microsatellites on each chromosome were analyzed in 164 cases of abortion. Eighty-three of the 164 cases had chromosomal abnormalities. In 79 of the remaining 81 cases with normal karyotypes, the microsatellite analysis revealed that biparental patterns were present in the informative microsatellites in all chromosomes. In one of the remaining two cases, however, the polymorphic patterns of chromosome 14 appeared to be both of paternal origin. The patterns of the distal of the long arm were homozygous, and those of the remaining region were heterozygous. That is, this fetus had paternal UPD 14, originating from meiosis I nondisjunction. In the other case, the polymorphic patterns of the distal one third of the long arm of chromosome 7 were uniparental (maternal) in origin whereas those of the remaining region of this chromosome were biparental. These findings thus suggested that this chromosome might have originated from chromatid exchange between the long arms of paternal and maternal chromosome 7 at the first mitotic division. Microsatellite analysis, however, produced no evidence of duplication or deletion of any segments. The findings also suggest the possibility that some UPDs may cause spontaneous abortion.
The Prader-Willi/Angelman Critical Region (PWACR; Chromosome 15q11-13) is of interest as a potential locus for genes conferring susceptibility to autism spectrum disorders (ASD). This report describes a female proband referred for evaluation of a possible ASD. Genetic analyses indicated that the proband, her father and one of her sisters, carried a paternally derived interstitial duplication involving 15q11-13. The proband showed evidence of ASD (PDD-NOS), borderline mental retardation, mild hypotonia and joint laxity. Her father and her sister were of normal intelligence and neither was thought to have an ASD, although speech/language difficulties and some autistic type behaviours were reported to have been present early in the development of the sister. This is one of the first reports of a child with a paternal duplication and an autism spectrum disorder. More research is required to determine whether paternally derived duplications that involve 15q11-13 are associated with developmental impairments.
An abundant acidic germinal vesicle protein of 100,000 Da has been previously described in Xenopus laevis and termed N1. It is supposed to bind stored histones in the oocyte. Species-specific monoclonal antibodies (mABs) have been raised against the oocyte nuclear protein of X. borealis B3, that is equivalent to protein N1 of X. laevis. These mABs have been used to monitor paternal gene expression of B3 in hybrids between X. laevis and X. borealis. Protein B3 is accumulated in oocyte nuclei, shed into the cytoplasm of the egg upon germinal vesicle breakdown, and reaccumulated by the nuclei of the embryo. During development it appears to be gradually diluted in all cells of the embryo, its levels falling below the limits of detection after stage 50. In interspecies hybrids, the paternal antigen is not found in somatic cells, as judged by immunohistological criteria. Therefore it has been concluded that protein B3 is not expressed from the genes of the embryo and that the maternal store of B3 is sufficient to endow the nuclei of the embryo with this protein up to the feeding tadpole stage. This deduction is corroborated by radiolabeling experiments. The paternal antigen B3 is, however, specifically expressed in the germ line. In hybrids and in X. borealis it is first detected in the nuclei of oogonia and spermatogonia, but, in both sexes, it is undetectable during early meiotic prophase. In female germ cells, accumulation of B3 is resumed at the beginning of diplotene, concomitant with the onset of oocyte growth. The significance of the observed cell specificity of B3 during germ cell differentiation is discussed in relation to its postulated function as a histone storage factor.
The two parental genomes lie separate within the zygote and may be differentially affected by environmental influences. We have shown earlier (Russell et al., 1988) that the maternal genome within the mouse zygote is exquisitely sensitive to the induction of point mutations by N-ethyl-N-nitrosourea (ENU), and that the initial lesion probably occurs in one strand of the DNA. The present experiment measured specific-locus mutation induction in the paternal genome. Zygotes containing a multiple-recessive maternal genome (a; b; p cch; d se; s) and the corresponding wild-type alleles in the paternal one were exposed to 50 mg ENU/kg in vivo at one of two stages: the presumed times of sperm entry and early pronuclear stage. At weaning age, the resulting mice were examined for mutations at the marked loci as well as for other mutations producing externally visible phenotypes. At the marked loci, one possible mosaic (for b) was observed among 2113 classified offspring that had been treated with ENU as zygotes; this animal failed to transmit a mutation. By contrast, in the reciprocal cross (which tests the maternal genome) we had observed 8 specific-locus mutations (6 of them mosaics) among 1555 offspring that had received the same dose of ENU during sperm entry (and completion of oocyte meiosis II). In the present experiment, we also found one mutation at other loci (two at other loci in the reciprocal cross). The frequency of offspring with small white belly spots was significantly greater in the treated groups (3.5 and 1.9% at the earlier and later stage, respectively) than in the control (1.0%), the excess being almost entirely due to daughters. Genetic tests of a large number of such offspring failed to find a genetic cause. Instead, it appears that this phenotype may be influenced by factors in the intrauterine environment. It is concluded that shortly after sperm entry, the paternal genome of the zygote is less sensitive than the maternal one to the induction of mutations by ENU.
Cord-blood monocytes (cord-blood M phi s) pulsed with Escherichia coli or tetanus toxoid had the ability to present antigen and to induce proliferation of antigen-specific paternal T cells. The magnitude of the proliferative response was comparable (86 +/- 14%) to that obtained after co-culturing paternal T cells with antigen-pulsed autologous M phi s. Cord-blood M phi s were surface Ia positive (54 +/- 12% as compared to 78 +/- 6% of adult M phi s), which correlated well with their ability to present antigen, but the experimental design was not suitable to show quantitative relationships. Compared to M phi s from the peripheral blood of adults, cord-blood M phi s released equal or larger amounts of interleukin 1 upon stimulation with E. coli. Immunoadsorption studies showed the capacity of cord-blood M phi s to specifically remove E. coli-reactive T cells from a paternal T-cell pool (65% of antigen reactivity could be removed). This indicated that cord-blood M phi s were able to express bacterial antigen in their membrane. These results provide evidence that human mononuclear phagocytes are mature at birth with respect to surface Ia expression, release of interleukin 1, and presentation of bacterial antigen.
Accuracy of assigning foal paternity to the second serving stallion for foals whose dams had been bred to two stallions within an interval of 1 to 45 days was investigated using breeding dates from 108 equine paternity cases solved by blood typing. One hundred two of the foals were sired by the second stallion but six foals (5.5%) were excluded as being by the second sires. Thus, breeding dates are not reliable as a sole source of information to assign equine paternity accurately.
Angelman's syndrome and Prader-Willi syndrome are both causes of mental retardation with recognisable, but quite different, clinical phenotypes. Both are associated with deletions of chromosome 15q11-13, of maternal origin in Angelman's and paternal in Prader-Willi. Prader-Willi can arise by inheritance of two chromosomes 15 from the mother and none from the father (uniparental maternal disomy). In 2 patients with Angelman's syndrome we found evidence of uniparental paternal disomy. The phenotypic effects of maternal and paternal disomy of chromosome 15 are very different and inheritance of two normal 15s from one parent does not lead to normal development--strong evidence in man for genomic imprinting, in which the same gene has different effects dependent upon its parental origin.
C57/B1 female mice (haplotype H2-b) were treated throughout their life cycles with rabbit anti-mouse IgM antibodies in order to remove all maturing B-lymphocytes. At an age of 40 days the B-cell-deprived mice and the corresponding controls were allowed to mate with CBA/Ca males (haplotype H2-k). Four groups of allopregnant animals were investigated: (A) mice not subjected to further treatment, which were allowed to pass through a first pregnancy, (B) mice not subjected to further treatment, which were allowed to pass through a first and second pregnancy, (C) mice immunized with paternal cells prior to mating and then allowed to pass through a first pregnancy, (D) mice which during their first pregnancy were given transfusions of anti-paternal lymphocytes obtained from hyperimmune virgin donors. All animals were dissected on the calculated day for parturition (or the first day that abortions or resorptions were detected). On conclusion of the experiments, the efficiency of the anti-IgM treatment was defined for each mouse, using three different methods (ELISA for detection of serum IgG, immune staining for detection of surface Ig-carrying cells, and the protein A plaque assay for detection of Ig-secreting cells). The T-cell function was recorded in vitro by ConA responsiveness. In addition, control animals were assayed for anti-paternal serum antibodies. In experiments (A), (B) and (C), B-cell-deprived mice and corresponding controls were equally successful in passing through pregnancy, having fairly similar litter sizes and resorption frequency. In group (D), however, some of the anti-IgM-treated mice resorbed all her fetuses. Those that gave birth at on schedule had a resorption frequency and litter size fairly similar to those of the controls.
Studies have been carried out on allogeneically mated pregnant female mice to examine the relationship between the levels of anti-paternal alloantibody occurring free or as soluble immune complexes in the maternal peripheral circulation and that existing in a bound form in the placenta and free in the fetal circulation. In a 'non-responder' strain of mouse, as defined by the inability to detect anti-paternal alloantibody in the peripheral serum of multiparous allogeneically mated females, no alloantibody could be detected as soluble immune complexes, bound to the placenta or in the fetal circulation. A similar situation existed in females of a 'responder' strain during their first pregnancy and in some individuals during their second. However, in 'responder' strain females possessing alloantibody in their peripheral serum, alloantibody could be eluted from the semi-allogeneic placenta when peripheral titres exceeded 1:16, and was found in the fetal serum when they exceeded 1:128. When such females were subsequently mated syngeneically, alloantibody was detected in placental eluates only when peripheral titres exceeded 1:128-256 and in the fetal serum when they exceeded 1:16. The alloantibody eluted from placentae and that found in neonatal serum exhibited similar isotype distribution to that in the peripheral serum. These results are discussed with reference to the relative importance of the yolk sac and the immunoabsorbent semi-allogeneic placenta in the restricted transfer of pregnancy-induced anti-paternal alloantibody to the fetus.
Active anti-paternal immunization does not compromise pregnancy in eutherian mammals. However, in an earlier study in a marsupial, grafting with paternal skin appeared to have resulted in transient infertility. In the present study, by critically monitoring the breeding efficiency of tammar wallabies sensitized against their mate's transplantation antigens, we aimed to resolve the question of immunologically mediated infertility in marsupials. Eight experimental females received two full-thickness skin grafts from their prospective mate and eight controls grafts of their own skin. The experimental group were monitored for 30 reproductive cycles and produced 24 pouch young (PY), whereas the control animals produced 28 young from 33 cycles. Five of the 11 apparently non-fertile cycles were judged to be normal pregnancies where the young had failed to reach the pouch (cycle length less than 28 days; rapid plasma progesterone decline coincident with oestrus). True infertility was thus limited and, although occurring mainly in the male-skin grafted group (5 cycles), this was not significantly different (chi 2, P greater than 0.5) from the controls (1 cycle) and represented the effect of one very poor breeder. We conclude that allogeneic pregnancy in marsupials is not compromised by active anti-paternal immunization. Infertility observed here, and in the earlier study, reflected disturbance of breeding owing to handling of the animals or the poor reproductive efficiency of individual animals in small experimental groups.
Paternalism is one of the most problematic ethical issues in public health promotion. In the article an attempt is made to elucidate the matter by examining the theoretical characteristics of paternalistic attitudes and action on the one hand, and actual Finnish anti-smoking policies on the other. The attitudes adopted by Finnish health authorities toward smoking are strongly paternalistic, i.e. based on the idea that the general public is not to be relied on in assessing the health risks of tobacco use. Surprisingly, however, the actual governmental anti-smoking measures in Finland cannot be truthfully described as overtly constraining. Since paternalism implies restrictions on personal freedom for the individual's own good, many branches of smoking control fall outside its proper scope: for instance, restrictions on smoking in public premises can almost always be justified by referring to the harm inflicted by smokers on the other people. But most of the Finnish governmental anti-smoking measures which can be classified as paternalistic are also justifiable. Some of them concern minors only or mainly minors, and thus can be defended as instances of authorities' parental concern for our children. Some are freedom-restricting but only in a weak sense and are based on the idea of informing people about the dangers of smoking, while leaving the final decision up to them. In the last analysis, there is but one regulation that meets the criteria of wrongful paternalism, and that one, the ban on strong tobacco brands, may not be important enough, in practice, to raise major ethical controversies.
BACKGROUND: Few studies have investigated the possible differential transmission of maternal and/or paternal coronary heart disease (CHD) to offspring, after accounting for sociodemographic characteristics. METHODS: The Multigeneration Register was linked to hospital data in this study of all Swedish individuals born since 1932 and their parents. Registered cases of CHD between January 1, 1987, and December 31, 2001, were evaluated. Poisson regression was used to calculate standardized incidence ratios (SIRs) for men and women with mothers and/or fathers affected by CHD compared with men and women whose parents were not affected. All analyses were conducted in 2005. RESULTS: Maternal transmission was stronger than paternal transmission and the confidence intervals did not overlap. For women, the overall SIRs were 1.43 (95% confidence interval [CI]=1.34-1.51) for maternal transmission and 1.17 (95% CI=1.11-1.23) for paternal transmission. For men, the corresponding SIRs were 1.55 (95% CI=1.50-1.60) and 1.41 (95% CI=1.37-1.45). Even higher SIRs were found in the youngest age groups, among those with both parents affected by coronary heart disease, and among those with premature parental CHD. CONCLUSIONS: These findings might ultimately influence treatment decisions regarding risk factors and suggest the need for research focusing on genetic and intrauterine risk factors.
BACKGROUND: Reported family medical history may be the most widely accessible genomics screen currently available. The worth of any population-screening tool may be measured by parameters such as sensitivity and specificity. There is some evidence and theory suggesting that family history of breast cancer may be more frequently communicated about maternal (versus paternal) lines. If true, a discrepancy in reporting family history of breast cancer could mean suboptimal accuracy for this genomics-screening tool. METHODS: A cross-sectional analysis of reported family history of breast cancer was conducted beginning in early fall 2005 of data collected from April 2003 to March 2005. Study participants were Women's Health Clinic patients without breast cancer aged at least 40 years. The number of women reporting extended paternal relatives (e.g., aunts, grandmothers) with breast cancer was compared to the number of women reporting maternal relatives. RESULTS: More women reported a maternal relative with breast cancer (16%) compared to those reporting paternal relatives (10%) (McNemar odds ratio = 1.71, 95% confidence interval = 1.26 to 2.34). A discrepancy remained in analyses adjusting for potential covariates (race/ethnicity, awareness of breast cancer, family communication about breast cancer, and perceived risk). CONCLUSIONS: Self-reported family history of breast cancer may not optimally capture inherited risk from the father's side of the family. Further research is needed to look for modifiable contributors to this discrepancy to optimize screening for familial breast cancer.
BACKGROUND: Although evolutionary novelty by gene duplication is well established, the origin and maintenance of essential genes that provide entirely new functions (neofunctionalization) is still largely unknown. Drosophila is a good model for the search of genes that are young enough to allow deciphering the molecular details of their evolutionary history. Recent years have seen increased interest in genes specifically required for male fertility because they often evolve rapidly. A special class of genes affecting male fertility, the paternal effect genes, have also become a focus of study to geneticists and reproductive biologists interested in fertilization and sperm-egg interactions. RESULTS: Using molecular genetics and the annotated Drosophila melanogaster genome, we identified CG14251 as the Drosophila paternal effect gene, ms(3)K81 (K81). This assignment was subsequently confirmed by P-element rescue of K81. A search for orthologous K81 sequences revealed that the distribution of K81 is surprisingly restricted to the 9 species comprising the melanogaster subgroup. Phylogenetic analyses indicate that K81 arose through duplication, most likely retroposition, of a ubiquitously expressed gene before the radiation of the melanogaster subgroup, followed by a period of rapid divergence and acquisition of a critical male germline-specific function. Interestingly, K81 has adopted the expression profile of a flanking gene suggesting that transcriptional coregulation may have been important in the neofunctionalization of K81. CONCLUSION: We present a detailed case history of the origin and evolution of a new essential gene and, in so doing, provide the first molecular identification of a Drosophila paternal effect gene, ms(3)K81 (K81).