Parental Incompatibility Research Articles

Does anti-HPA-1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) ensues from parental incompatibility for platelet alloantigens with maternal sensitization. HPA-1a/1b incompatibility is the most common cause of FNAIT in Caucasians. Placental villitis and lower birthweight in FNAIT suggest anti-HPA-1a may have effects beyond inducing thrombocytopenia. Does FNAIT secondary to anti-HPA-1a result in smaller newborns and, the corollary, does antenatal management of FNAIT increase birthweight? Birthweights of 270 FNAIT-affected newborns from a randomized clinical trial and a NAITbabies.org survey (135 paired siblings) were compared with those of published controls and treated to untreated FNAIT-affected siblings. Birthweights were converted to percentiles to account for gestational age, sex, and role of birth order in birth weight. Body weights of FNAIT-affected and -unaffected pups in a mouse FNAIT model were analyzed. Untreated siblings in both the clinical trial and NAITbabies.org cohorts were not small, compared with normal controls. However, treated siblings in both cohorts had significantly higher birthweight percentiles compared with their previous untreated affected sibling. After accounting for gestational age, sex, and birth order, increased birthweight percentile in treated compared with the untreated siblings remained significant in both cohorts. FNAIT-affected neonatal mice had lower bodyweights than FNAIT-unaffected pups. Untreated FNAIT-affected newborns were not small; however, treatment of FNAIT-affected pregnancies increased newborn birthweights despite corrections to account for other factors that might have influenced the results. High dose IVIG is believed to "block" FcRn and lower maternal anti-HPA-1a levels, and thus increase birthweights by reducing levels of maternal anti-HPA-1a and reducing placental villitis.

Identifying Pregnancies at Higher Risk for HPA-1a Alloimmunization and Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT): An International, Prospective, Natural History Study

Background and significance Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from parental incompatibility of human platelet antigen (HPA) and subsequent maternal sensitization. When this occurs, fetal platelet production is impaired and platelet destruction accelerated. FNAIT is the platelet counterpart of Rhesus disease (RhD); however, FNAIT is rarer, more often occurs in first pregnancies, and alloimmunization may be detected as early as the 2nd trimester. Clinical presentation of FNAIT ranges from no/mild symptoms to severe thrombocytopenia and intracranial hemorrhage, which can take place in the second trimester and cause death or lifelong neurological impairment. Severe FNAIT outcomes impose substantial emotional and financial burden on affected families and healthcare systems. Among pregnant HPA-1a-negative women bearing an HPA-1a-positive fetus at risk of alloimmunization, ~27% carry the HLA-DRB3*01:01 gene variant, increasing sensitization risk ~25 fold and thus leading to much higher FNAIT risk. Screening for FNAIT in pregnancy is not routinely performed, unlike in RhD, resulting in failure to identify at-risk pregnancies prior to birth. To prevent severe FNAIT outcomes, we believe at-risk pregnancies must be identified very early in the second trimester, and prophylactic interventions started immediately. Current management of women with existing alloimmunization due to a prior FNAIT-affected pregnancy involves months of weekly antenatal intravenous immunoglobulin with or without steroid administration. Although fetal platelet counts often improve, this therapy is very burdensome to patients. Most data on FNAIT prevalence and risk are from Caucasian populations; studies in non-Caucasian populations have been too small to be informative. This is the first epidemiological study that seeks to identify HPA-1a-based FNAIT in a racially and ethnically diverse international population of pregnant women. Data to be tracked are: frequency of DRB3*0101 in HPA-1bb women; anti-HPA-1a alloimmunization; pregnancy outcomes; and neonatal thrombocytopenia. These data will provide a contemporary control population preceding future single-arm studies of a novel human anti-HPA-1a monoclonal antibody, RLYB212, in prophylaxis of maternal HPA-1a alloimmunization and FNAIT. The virtual elimination of RhD by screening of all pregnancies and administration of prophylaxis in at-risk cases remains one of the most significant medical advances ever achieved and provides a roadmap for FNAIT. Study design and methods Prospective, non-interventional, natural-history study assessing HPA-1a alloimmunization in pregnant women, conducted across multiple European centers in Norway, Netherlands, UK, and Germany, and in the USA. It will provide insights into anti-HPA-1a-mediated FNAIT risk and frequency among Caucasian and non-Caucasian pregnant women. Up to 30,000 women will be screened at gestational weeks 10-14 to enable early identification and follow-up of those women at higher alloimmunization risk, so that in the future, prophylaxis of the higher-risk women could be initiated. Informed consent will be requested for blood-sample collection at the 10-14 week visit for evaluation of FNAIT risk. Inclusion criteria Pregnant women aged ≥18 years Exclusion criteria Prior history of FNAIT or known HPA-1a alloimmunization Statistical methods Demographic, baseline characteristics and discrete variables will be summarized Primary objective To inform frequency of higher FNAIT risk among pregnant women of diverse racial and ethnic characteristics (all comers). (Figure) Secondary objectives Frequency of HPA-1a maternal alloimmunization at Weeks 10-14 postpartum in pregnant women at higher FNAIT risk and outcomes such as: - Spontaneous abortion: non-deliberate fetal death prior to 19 weeks of gestation - Elective abortion: deliberate termination of pregnancy at any time in gestation - Stillbirth: non-deliberate fetal death after 19 weeks of gestation - Premature birth: live birth prior to 37 completed weeks of gestation - Live births: ≥37 completed weeks of gestation Neonatal and severe neonatal thrombocytopenia: platelet count <150 × 10 9/L and <50 × 10 9/L, respectively, within 72 hours of birth Current status Enrolment for clinical-trial NCT05345561 is ongoing and expected to continue for ~3 years.

Analysis on fertility and inheritance of hybrid male sterility of indica rice 9814HS-1

Hybrid rice has generally a yield-increasing heterosis of 10%−15% compared with inbred parents. Food and Agriculture Organization (FAO) has recommended hybrid rice as one of the best choices for solving the food shortage in the developing countries. Male sterility provides a basic genetic tool for hybrid rice breeding. Hybrid male sterility refers to the phenomenon that F1 hybrid from two parents is abnormal or nonfunctional in the development of male organs. A new germplasm source of hybrid male sterility is valuable for establishing a novel system for using heterosis by hybrid breeding of three-way crossing, which helps to develop elite hybrid rice with better comprehensive traits. To date, hybrid male sterility occurs commonly from the crosses between species (e.g. Oryza rufipogon × Oryza sativa ) or subspecies (e.g. indica rice × japonica rice). Nevertheless, it is not clear if the hybrid male sterility could be induced from a cross within a subspecies. Here, we reported firstly the hybrid male sterility resulted from a cross between two indica rice parents, i.e., two WA-type maintainer lines of indica rice T98B and M114B. The InDel marker analysis showed that T98B and M114B had an indica -genotype frequency at 0.94 and 1.00, respectively, indicating both of them belong to indica rice. Field observation showed that 9814HS-1, the F1 hybrid of T98B (as female parent) and M114B (as male parent), was eco-typically male sterile. The pollens of 9814HS-1 were completely aborted, resulting in a seed setting rate at 0.00% when heading after early October at Changsha or before mid-March at Sanya, while both parents T98B and M114B were normally fertile under the same conditions. Interestingly, when T98B and M114B were crossed with eight other indica rice varieties, all of their F1 hybrids were normally fertile with a seed setting rate ranged from 80.35% to 91.87%, implying that the hybrid male sterility of 9814HS-1 is induced from the specific parental incompatibility between T98B and M114B. The restorability test showed that 9814HS-1 could be restored for fertility by all of six representative indica rice lines, with seed setting rates ranged from 85.24% to 93.21% in their F1 hybrids, indicating that the broad spectrum of restorability of 9814HS-1. This male sterility provides a good basis for hybrid breeding of three-way cross. Genetic analysis showed that both of the F1 hybrid and its reciprocal cross from T98B and M114B were male sterile, suggesting the hybrid male sterility was controlled by nuclear genes. The Chi-square test supported that the separation ratio of sterile: Fertile plants in both F2 and BC1F1 populations was confirmed to be 1:3, which we infer that the hybrid male sterility in 9814HS-1 is controlled by two pairs of non-allelic nuclear genes and occurs only when they are in a heterozygous state. This study provides a new perspective for re-recognizing rice reproductive barriers and opens up a new way for the multiple-line hybrid rice breeding.

Clonal structure and variable fertilization success in Florida Keys broadcast-spawning corals

Keystone reef-building corals in the Caribbean are predominantly self-incompatible broadcast spawners and a majority are threatened due to both acute adult mortality and poor recruitment. As population densities decline, concerns about fertilization limitation and effective population size in these species increase and would be further exacerbated by either high clonality or gametic incompatibility of parental genotypes. This study begins to address these concerns for two Caribbean broadcasting species by characterizing clonal structure and quantifying experimental pairwise fertilization success. Orbicella faveolata showed surprisingly high and contrasting levels of clonality between two sampled sites; Acropora palmata was previously known to be highly clonal. Individual pairwise crosses of synchronously spawning genotypes of each species were conducted by combining aliquots of gamete bundles immediately after spawning, and showed high and significant variability in fertilization success. Over half of the individual crosses of O. faveolata and about one-third of A. palmata crosses yielded ≤ 40% fertilization. Total sperm concentration was quantified in only a subset of O. faveolata crosses (range of 1–6 × 107 mL−1), but showed no correlation with fertilization success. We interpret that both parental incompatibility and individual genotypes with low-quality gametes are likely to have contributed to the variable fertilization observed with important implications for conservation. Differential fertilization success implies effective population size may be considerably smaller than hoped and population enhancement efforts need to incorporate many more parental genotypes at the patch scale to ensure successful larval production than indicated by estimates based simply on preserving levels of standing genetic diversity.

Bet-hedging as a mechanism for the evolution of polyandry, revisited.

Females that mate with multiple males (polyandry) may reduce the risk that their eggs are fertilized by a single unsuitable male. About 25 years ago it was hypothesized that bet-hedging could function as a mechanism favoring the evolution of polyandry, but this idea is controversial because theory indicates that bet-hedging via polyandry can compensate the costs of mating only in small populations. Nevertheless, populations are often spatially structured, and even in the absence of spatial structure, mate-choice opportunity can be limited to a few potential partners. We examined the effectiveness of bet-hedging in such situations with simulations carried out under two scenarios: (1) intrinsic male quality, with offspring survival determined by male phenotype (male's ability to generate viable offspring), and (2) genetic incompatibility (offspring fitness determined nonadditively by parental genotypes). We find higher fixation probabilities for a polyandrous strategy compared to a monandrous strategy if complete reproductive failure due to male effects or parental incompatibility is pervasive in the population. Our results also indicate that bet-hedging polyandry can delay the extinction of small demes. Our results underscore the potential for bet-hedging to provide benefits to polyandrous females and have valuable implications for conservation biology.

Is children's Body Mass Index associated with their parents' personality? A prospective controlled trial.

The aim of this study was to elucidate the effect of the personal characteristics and psychological status of parents on their children's Body Mass Index (BMI) by using validated questionnaires. Obese and healthy control group was assessed with The Parental Attitude Research Instrument (PARI) for the evaluation of parental attitudes towards their children. Additionally, Depression Anxiety and Stress Scale (DASS) were used to assess the relationships between parental depression, anxiety, stress and childhood obesity. A total of 105 children and their parents were divided into two groups. The study group consisted of 58 children with a BMI of higher than 85th percentile whereas 47 children with normal BMI (<85th percentile) were included as the control group. In both groups, the BMI of mothers which is between 25-and 30 kg/m2 and >30 kg/m2 had significant impact on the risk of children's obesity status 1.12-fold and 3.68-fold respectively. The PARI results provided that the children who had disciplined, over-protective parents and those in the parental incompatibility group had higher risk of being obese. Analysis of the DASS Test results showed that children having depressed parents had significantly higher risk of obesity than children whose parents were not depressed (P<0.05). Our results provided that, the parent's status such as obesity, depression and strict personal behaviors have negative impact on their children's weight which is resulting with obesity.

Female segregation patterns of the putative Y‐chromosome‐specific microsatellite markers INRA124 and INRA126 do not support their use for cattle population studies

Here we tested the segregation and paternal compatibility of markers INRA124 and INRA126 on female DNA in 10 different cattle families, in order to clarify the usefulness of these microsatellites for the study of male-mediated population processes in cattle. Their performance was compared with that of four microsatellites located in the PAR-BTAY (UMN0108, UMN0803, UMN0929 and UMN0905) and another one male-specific microsatellite (INRA189). INRA124 and INRA126 amplified the same sized fragment in both sexes. Same size alleles were sequenced and the high homology found allowed us to rule out non-specific female amplification. INRA124 showed full parental compatibility, whilst the locus INRA126 showed 55% parental incompatibility. Based on these observations, it is recommended that markers INRA124 and INRA126 should not be used in studies to characterize male-mediated genetic events in cattle.

Fetal and neonatal alloimmune thrombocytopenia: progress and ongoing debates

Fetal and neonatal alloimmune thrombocytopenia (AIT) is a result of a parental incompatibility of platelet-specific antigens and the transplacental passage of maternal alloantibodies against the platelet antigen shared by the father and the fetus. It occurs in approximately 1 in 1000 live births and is the most common cause of severe thrombocytopenia in fetuses and term neonates. As screening programs are not routinely performed, most affected fetuses are identified after birth when neonatal thrombocytopenia is recognized. In severe cases, the affected fetus is identified as a result of suffering from an in utero intracranial hemorrhage. Once diagnosed, AIT must be treated antenatally as the disease can be more severe in subsequent pregnancies. While there have been many advances regarding the diagnosis and treatment of AIT, it is still difficult to predict the severity of disease and which therapy will be effective.

Massive fetal hemorrhage and fetomaternal alloimmune thrombocytopenia from human platelet antigen 5b incompatibility: an unusual association

Massive fetal hemorrhage and fetomaternal alloimmune thrombocytopenia from human platelet antigen 5b incompatibility: an unusual association

The use of the isoenzymic marker gene Got-1 in the recognition of incompatibility S alleles in apple

The S incompatibility system of apple was confirmed through the application of the gene Got-1 for glutamate oxaloacetate transaminase as a marker for the S locus. The 11S alleles proposed by Kobel et al. (1939) were confirmed through anomalous segregations for Got-1 observed in 14 semi-compatible crosses and regular segregations observed in 2 fully compatible crosses. The S allele genotypes of 'Idared' (S 3 S 7), 'Cox' (S 5 S 9) and 'Fiesta' (S 3 S 5) were determined and found to fall within the original series. By associating parental incompatibility genotypes with the segregation of Got-1 alleles, we were able to deduce the coupling of S and Got-1 alleles in 9 varieties.

To breed or not to breed: causes and implications of non-breeding habit in the willow tit Parus montanus.

Causes and consequences of non-breeding in willow tits were studied in northern Finland during 1986-1992. The breeding status was sex and age biased; males and yearling birds were in excess among the non-reproducers. Due to sex bias in the population it appeared detrimental for males to lose a mate, especially shortly before breeding. Lack of a mate was a important factor for males not reproducing (37% of non-breeding males) than for females (14%). Most of the non-breeding birds maintained a pair bond which only rarely broke up for the next breeding season (divorce rate 5.5%). This implies that parental incompatibility is not a possible explanation for pairs not reproducing. Males that did not breed tended to survive better than reproducing ones, whereas such a relationship was not found for females. It is possible that this sex-related difference in survival cost is attributable to quality differences among non-breeding individuals. It was especially low-quality yearling females, with low survival prospects, that were responsible for the discrepancy. The proportion of non-breeding females in the population correlated highly with clutch size and subsequent juvenile survival. It is therefore suggested that for most of these females non-breeding is a phenotypic response to low offspring value in the prevailing circumstances (inter-generational tradeoff). However, it is uncertain whether willow tits in a northern population can use breeding density as an indicator of changing survival prospects of their descendants, as suggested by Ekman and Askenmo (1986) for southern Sweden.

Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum.

Malarial parasites have two highly conserved cytoplasmic DNA molecules: a 6-kb tandemly arrayed DNA that has characteristics of a mitochondrial genome, and a 35-kb circular DNA that encodes functions commonly found in chloroplasts. We examined the inheritance pattern of these elements in two genetic crosses of Plasmodium falciparum clones. Parent-specific oligonucleotide probes and single-strand conformation polymorphism analysis identified single nucleotide changes that distinguished the parental 6- and 35-kb DNA molecules in the progeny. In all 16 independent recombinant progeny of a cross between a Central American clone, HB3, and a Southeast Asian clone, Dd2, the 6- and 35-kb DNAs were inherited from the Dd2 parent. In all nine independent recombinant progeny of a cross between clone HB3 and a likely African clone, 3D7, the 6-kb DNA was inherited from the 3D7 parent. Inheritance of cytoplasmic genomes of the Dd2 and 3D7 parents was, therefore, dominant over that of the HB3 parent. Cytoplasmic DNA molecules were found almost exclusively in the female gametes of malarial parasites; hence, clone HB3 did not appear to have served as a maternal parent for the progeny of two crosses. Defective differentiation into male gametes by clone Dd2 is likely to be a reason for the cytoplasmic inheritance pattern seen in the HB3 x Dd2 cross. However, incompetence of male or female gametes is unlikely to explain the uniparental dominance in recombinant progeny of the HB3 x 3D7 cross, since both parents readily self-fertilized and completed the malaria life cycle on their own. Instead, the data suggest unidirectional parental incompatibility in cross-fertilization of these malarial parasites, where a usually cosexual parental clone can participate only as a male or as a female. Such an incompatibility may be speculated as indicating an early phase of reproductive isolation of P. falciparum clones from different geographical regions.

Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum.

Malarial parasites have two highly conserved cytoplasmic DNA molecules: a 6-kb tandemly arrayed DNA that has characteristics of a mitochondrial genome, and a 35-kb circular DNA that encodes functions commonly found in chloroplasts. We examined the inheritance pattern of these elements in two genetic crosses of Plasmodium falciparum clones. Parent-specific oligonucleotide probes and single-strand conformation polymorphism analysis identified single nucleotide changes that distinguished the parental 6- and 35-kb DNA molecules in the progeny. In all 16 independent recombinant progeny of a cross between a Central American clone, HB3, and a Southeast Asian clone, Dd2, the 6- and 35-kb DNAs were inherited from the Dd2 parent. In all nine independent recombinant progeny of a cross between clone HB3 and a likely African clone, 3D7, the 6-kb DNA was inherited from the 3D7 parent. Inheritance of cytoplasmic genomes of the Dd2 and 3D7 parents was, therefore, dominant over that of the HB3 parent. Cytoplasmic DNA molecules were found almost exclusively in the female gametes of malarial parasites; hence, clone HB3 did not appear to have served as a maternal parent for the progeny of two crosses. Defective differentiation into male gametes by clone Dd2 is likely to be a reason for the cytoplasmic inheritance pattern seen in the HB3 x Dd2 cross. However, incompetence of male or female gametes is unlikely to explain the uniparental dominance in recombinant progeny of the HB3 x 3D7 cross, since both parents readily self-fertilized and completed the malaria life cycle on their own. Instead, the data suggest unidirectional parental incompatibility in cross-fertilization of these malarial parasites, where a usually cosexual parental clone can participate only as a male or as a female. Such an incompatibility may be speculated as indicating an early phase of reproductive isolation of P. falciparum clones from different geographical regions.

Correlates of Perceived Parental Favoritism

Abstract A questionnaire study of over 600 male and female high school students (intact families and with at least one sibling) explored the phenomenon of parental favoritism. About half the respondents perceived the existence of favoritism on the part of one or both of their parents. Girls more often than boys were perceptive of such favoritism. The youngest child in the family was more often the favorite of the mother and the middle child was least often a parental favorite. Parental favoritism was associated with perceived parental incompatibility. Teenagers who perceived a sibling as being favored evidenced increased angry and depressive feelings as well as identity confusion. This latter effect was most pronounced when a parent of the same sex favored a sibling of the same sex as the respondent.