Parental Inbreeding Research Articles

The Combination of Mind and Brain Alteration in A Resource-Limited Country: Autism Spectrum Disorders and Epilepsy in A Child Psychiatry Unit in Dakar

Purpose of the study: Autism spectrum disorders (ASD) and epilepsy can coexist in the same person, constituting poor bilateral prognosis factors. This study describes the sociodemographic elements of patients with ASD and studies the clinico-paraclinical aspects of their epilepsy and its evolution in 2003. Patients and Methods: Cross-sectional and descriptive study in Child psychiatry at CHNU Fann, with analysis of the files of all patients followed between January 2004 and September 2018 for ASD with/without epilepsy. We used a standardized survey with several items. Results: Forty -five patients with ASD collected, with an epileptic frequency of 37.8%. The main history was fetal suffering (24.4%) and parental inbreeding (22.2%). Most of the symptoms of ASD were seen before 3 years old (66.6%) and epilepsy started before 5 years (94%). Seizures were generalized (58.8%), mainly tonic-clonic (80%) or focal (35.3%), with a frequency of 2 seizures / day at 1 seizure / week. The EEG showed abnormalities in frontal areas in 60%, and Centro-parietal in 26.6%. Brain imaging and evoked auditory potential were normal respectively in 93.9%, and 87.2%. Management was multimodal for ASD (neuropsychological, psychomotor, speech therapy) and medicated for epilepsy, mainly by monotherapy (82.4%) with Valproate (58.8%), Phenobarbital (17.6). Forty percent of patients were out of school and 55.6% in primary school. Twenty-five patients were self-reliant to moderately independent, mainly the epileptics (60%). The 2023 evaluation of this cohort concerns 60% of patients with epilepsy in complete remission and behavioral and language stability under continuous management. Conclusion: We find a statistic difference by age between epilepsy and ASD with a genetic predisposition related to parental inbreeding and a family history of ASD and epilepsy and to a lesser extent the existence of acute fetal suffering. The contribution of EEG was significant with a predilection of frontal abnormalities whose epileptic treatment appears to improve the impact in children's behavioral disorders.

Mate selection: A useful approach to maximize genetic gain and control inbreeding in genomic and conventional oil palm (Elaeis guineensis Jacq.) hybrid breeding.

Genomic selection (GS) is an effective method for the genetic improvement of complex traits in plants and animals. Optimization approaches could be used in conjunction with GS to further increase its efficiency and to limit inbreeding, which can increase faster with GS. Mate selection (MS) typically uses a metaheuristic optimization algorithm, simulated annealing, to optimize the selection of individuals and their matings. However, in species with long breeding cycles, this cannot be studied empirically. Here, we investigated this aspect with forward genetic simulations on a high-performance computing cluster and massively parallel computing, considering the oil palm hybrid breeding example. We compared MS and simple methods of inbreeding management (limitation of the number of individuals selected per family, prohibition of self-fertilization and combination of these two methods), in terms of parental inbreeding and genetic progress over four generations of genomic selection and phenotypic selection. The results showed that, compared to the conventional method without optimization, MS could lead to significant decreases in inbreeding and increases in annual genetic progress, with the magnitude of the effect depending on MS parameters and breeding scenarios. The optimal solution retained by MS differed by five breeding characteristics from the conventional solution: selected individuals covering a broader range of genetic values, fewer individuals selected per full-sib family, decreased percentage of selfings, selfings preferentially made on the best individuals and unbalanced number of crosses among selected individuals, with the better an individual, the higher the number of times he is mated. Stronger slowing-down in inbreeding could be achieved with other methods but they were associated with a decreased genetic progress. We recommend that breeders use MS, with preliminary analyses to identify the proper parameters to reach the goals of the breeding program in terms of inbreeding and genetic gain.

Parental breeding decisions and genetic quality predict social structure of independent offspring.

Across the animal kingdom, newly independent juveniles form social associations that influence later fitness, mate choice and gene flow, but little is known about the ontogeny of social environments, particularly in wild populations. Here we test whether associations among young animals form randomly or are influenced by environmental or genetic conditions established by parents. Parents' decisions determine natal birth sites, which could affect who independent young initially encounter; secondly, mate choice determines genetic condition (e.g. inbreeding) of young and the parental care they receive, which can affect sociability. However, genetic and environmental factors are confounded unless related offspring experience different natal environments. Therefore, we used a long-term genetic pedigree, breeding records and social network data from three cohorts of a songbird with high extra-pair paternity (hihi, Notiomystis cincta) to disentangle (1) how nest location and relatedness contribute to association structure once juveniles disperse away from birth sites, and (2) if juvenile and/or parental inbreeding predicts individual sociability. We detected positive spatial autocorrelation: hihi that fledged closer by were more likely to associate even after dispersing, irrespective of genetic relatedness. Juvenile inbreeding did not predict sociability, but those raised by more inbred fathers formed more, stronger, associations, which did not depend on whether that male was the genetic parent or not. These results suggest that the natal environment created by parents, rather than focal genetic condition, establishes the foundation for social associations. Overall, we highlight how social inheritance may play an important role in population dynamics and evolutionary potential in wild animals.

Inbreeding depression in an outbred stickleback population.

Inbreeding depression refers to the reduced fitness of offspring produced by genetically-related individuals and is expected to be rare in large, outbred populations. When it occurs, marked fitness loss is possible as large populations can carry a substantial load of recessive harmful mutations which are normally sheltered at the heterozygous state. Using experimental cross data and genome-wide identity-by-descent (IBD) relationships from an outbred marine nine-spined stickleback (Pungitius pungitius) population, we documented a significant decrease in offspring survival probability with increasing parental IBD sharing associated with an average inbreeding load (B) of 10.5. Interestingly, we found that this relationship was also underlined by a positive effect of paternal inbreeding coefficient on offspring survival, suggesting that certain combinations of parental inbreeding and genetic relatedness among mates may promote offspring survival. Our results demonstrate the potential for substantial inbreeding load in an outbred population and emphasize the need to consider fine-scale genetic relatedness in future studies of inbreeding depression in the wild.

An Impressive Case Report of Pachyonychia Congenita and Short Literature Review

Aims: Pachyonychia congenita is a rare genodermatosis related to mutations in the genes encoding keratins. Illustrations of such a typical case of this uncommon condition have rarely been seen in the literature, hence the interest of our case report.
 Case Report: An 11-year-old girl with a history of parental inbreeding presented with painful bilateral plantar hyperkeratosis associated with significant pachyonychia of the 20 nails and other clinical signs supporting the diagnosis of pachyonychia congenita.
 Discussion: Pachyonychia congenita is an autosomal dominant inherited dyskeratosis due to a mutation in the keratin genes k6a, k6b, k6c, k16 or k17. Clinical signs are dominated by pachonychia and painful palmoplantar keratoderma impacting patients' quality of life. The association with other disorders is possible. To date, treatment remains symptomatic.
 Conclusion: The diagnosis of congenital pachyonychia is based on the genetic study of the mutations involved. Nevertheless, a clinical presentation as suggestive as ours allows the immediate diagnosis, thus making this article interesting.

Self-Fertilization, Inbreeding, and Yield in Alfalfa Seed Production.

Selfing (self-pollination) is the ultimate form of inbreeding, or mating among close relatives. Selfing can create yield loss when inbreeding depression, defined as a lower survival and reproduction of inbred relative to outbred progeny, is present. To determine the impact of selfing in alfalfa (Medicago sativa L.), we quantified the selfing rate of 32 alfalfa seed production fields located in three regions, namely, the Pacific Northwest (PNW), the Central Valley of California (CEV), and the Imperial Valley of California (IMP). Selfing rates (the proportion of selfed seeds) varied between 5.3 and 30% with an average of 12.2% over the 32 seed production fields. In both the parents and their progeny, we observed an excess of heterozygotes relative to Hardy–Weinberg expectations. We detected notable levels of inbreeding in parents (0.231 ± 0.007 parental inbreeding coefficient) and progeny (0.229 ± 0.005). There were a 15% decrease in the number of seeds per stem (seed set) and a 13% decline in the number of seeds per pod in selfed relative to outcrossed stems, but negligible inbreeding depression for pods per raceme and seed weight. The number of racemes on selfed stems increased significantly in fields with greater selfing rates, supporting the presence of geitonogamous or among flower selfing. Despite the significant level of inbreeding depression, seed set did not decrease in fields with higher selfing rates, where the greater number of racemes on the selfed stems increased the seed set. The effects of the field selfing rate on the seed yield metrics were mostly indirect with direct effects of the number of racemes per stem. Available data indicate that the majority of selfing in alfalfa is pollinator-mediated, and thus, eliminating selfing in alfalfa seed production would require the selection of self-incompatible varieties, which, by eliminating inbreeding depression, would provide a 15% potential increase in seed yield and an increase in future hay yield.

Close‐kin mating, but not inbred parents, reduces hatching rates and offspring quality in a threatened tortoise

Inbreeding depression, the reduction in fitness due to mating of related individuals, is of particular conservation concern in species with small, isolated populations. Although inbreeding depression is widespread in natural populations, long-lived species may be buffered from its effects during population declines due to long generation times and thus are less likely to have evolved mechanisms of inbreeding avoidance than species with shorter generation times. However, empirical evidence of the consequences of inbreeding in threatened, long-lived species is limited. In this study, we leverage a well-studied population of gopher tortoises, Gopherus polyphemus, to examine the role of inbreeding depression and the potential for behavioural inbreeding avoidance in a natural population of a long-lived species. We tested the hypothesis that increased parental inbreeding leads to reduced hatching rates and offspring quality. Additionally, we tested for evidence of inbreeding avoidance. We found that high parental relatedness results in offspring with lower quality and that high parental relatedness is correlated with reduced hatching success. However, we found that hatching success and offspring quality increase with maternal inbreeding, likely due to highly inbred females mating with more distantly related males. We did not find evidence for inbreeding avoidance in males and outbred females, suggesting sex-specific evolutionary trade-offs may have driven the evolution of mating behaviour. Our results demonstrate inbreeding depression in a long-lived species and that the evolution of inbreeding avoidance is shaped by multiple selective forces.

The Effect of Parental Consanguinity and Inbreeding on the Anthropometric Measurements of Children

The Effect of Parental Consanguinity and Inbreeding on the Anthropometric Measurements of Children

Factors influencing litter size and puppy losses in the Entlebucher Mountain dog

A good reproductive performance is a central element of animal breeding. The breeders of Entlebucher Mountain dogs observed a decrease of the mean litter size and an increase of the number of unsuccessful matings in the past years. The aim of the present study was to identify factors with an influence on fertility in this breed. In total, 915 litters from 202 sires and 348 dams from 1986 to 2013 entered the analyses. The total puppy losses (7.4%) reduced the mean litter size at birth of 5.49 ± 2.13 to a mean litter size at registration of 5.08 ± 2.05. There was no deviation from the expected equal sex distribution for puppies at birth and at registration, as well as for puppy losses consisting of stillborn puppies and puppies which died or had to be euthanized before registration. The mean annual litter inbreeding coefficient increased from 0.37 in 1986 to 0.40 in 2013 and was correlated with the year of birth of the litter (Kendall's tau b = 0.46). The age of the dam and parental inbreeding were identified as significant predictors with a negative effect on litter size at birth. For the litter size at registration the age and inbreeding of the dam had a significant negative effect and a 1% increase of dam inbreeding is expected to decrease the litter size at birth and registration by 0.1 and 0.09 puppies, respectively. The occurrence of total puppy losses decreased during the years and was more frequent in larger litters. In addition, in litters of older parents the occurrence of puppy losses was more frequent than in litters from younger parents. The final generalized linear mixed-effects models for litter size at birth, litter size at registration and for total puppy losses explained 36%, 33% and 22% of the total variance, respectively. The impact of inbreeding and parental age on fertility of the Entlebucher Mountain dog was small and the influence of the dam was much bigger than the one of the sire. Other factors must be responsible for the variability of litter sizes not explained by the models. Without changes of breeding circumstances, a further increase of inbreeding must be expected. Therefore, a close monitoring and minimizing of inbreeding must be followed up by the breeding community.

Whole-exome sequencing to analyze population structure, parental inbreeding, and familial linkage

Principal component analysis (PCA), homozygosity rate estimations, and linkage studies in humans are classically conducted through genome-wide single-nucleotide variant arrays (GWSA). We compared whole-exome sequencing (WES) and GWSA for this purpose. We analyzed 110 subjects originating from different regions of the world, including North Africa and the Middle East, which are poorly covered by public databases and have high consanguinity rates. We tested and applied a number of quality control (QC) filters. Compared with GWSA, we found that WES provided an accurate prediction of population substructure using variants with a minor allele frequency > 2% (correlation = 0.89 with the PCA coordinates obtained by GWSA). WES also yielded highly reliable estimates of homozygosity rates using runs of homozygosity with a 1,000-kb window (correlation = 0.94 with the estimates provided by GWSA). Finally, homozygosity mapping analyses in 15 families including a single offspring with high homozygosity rates showed that WES provided 51% less genome-wide linkage information than GWSA overall but 97% more information for the coding regions. At the genome-wide scale, 76.3% of linked regions were found by both GWSA and WES, 17.7% were found by GWSA only, and 6.0% were found by WES only. For coding regions, the corresponding percentages were 83.5%, 7.4%, and 9.1%, respectively. With appropriate QC filters, WES can be used for PCA and adjustment for population substructure, estimating homozygosity rates in individuals, and powerful linkage analyses, particularly in coding regions.

Resolving the conundrum of inbreeding depression but no inbreeding avoidance: Estimating sex-specific selection on inbreeding by song sparrows (Melospiza melodia)

Inbreeding avoidance among interacting females and males is not always observed despite inbreeding depression in offspring fitness, creating an apparent “inbreeding paradox.” This paradox could be resolved if selection against inbreeding was in fact weak, despite inbreeding depression. However, the net magnitude and direction of selection on the degree to which females and males inbreed by pairing with relatives has not been explicitly estimated. We used long‐term pedigree data to estimate phenotypic selection gradients on the degree of inbreeding that female and male song sparrows (Melospiza melodia) expressed by forming socially persistent breeding pairs with relatives. Fitness was measured as the total numbers of offspring and grand offspring contributed to the population, and as corresponding expected numbers of identical‐by‐descent allele copies, thereby accounting for variation in offspring survival, reproduction, and relatedness associated with variation in parental inbreeding. Estimated selection gradients on the degree to which individuals paired with relatives were weakly positive in females, but negative in males that formed at least one socially persistent pairing. However, males that paired had higher mean fitness than males that remained socially unpaired. These analyses suggest that net selection against inbreeding may be weak in both sexes despite strong inbreeding depression, thereby resolving the “inbreeding paradox.”

Consanguineous matings among Egyptian population

Consanguinity is the blood relationship that exists among individuals that descend from a common ancestor. The objectives of the study was to explore the frequency and socio-economic determinants of consanguinity in Egypt. The study was carried out using a cross-sectional approach which included 10,000 unselected couples. All couples were recruited from the prenatal, gynecologic, neonatal and pediatric clinics as well as vaccination centers in three hospitals one in Lower Egypt (Cairo) and two in Upper Egypt (Sohag and Assuit). Consanguineous marriage is still high in Egypt (35.3%), especially among first cousins (86%). However the frequency varies by region. It is higher in Sohag (42.2%) and Cairo (36.1%) than in Assuit (21.7%). Also it was higher in rural areas (59.9%) than in semi-urban and urban areas (23.5% and 17.7%, respectively). It was associated with decreased age of marriage, low educational level and unemployment in the couples which means that the socio-economic determinants are still working in maintaining this high rate of consanguinity. This is in addition to the high divorce rate and increased number of unmarried females in Egypt. Advances in genetics have led to a deeper understanding of the effect of inbreeding on the occurrence of genetic diseases. As prolonged parental inbreeding has led to a background of homozygosity above that predicted by simple models of consanguinity, we encourage counselors to call on a reliable computer program for calculation of the recurrence risks in these families.

Technical Note: Recursive Algorithm for Inbreeding Coefficients Assuming Nonzero Inbreeding of Unknown Parents

A recursive algorithm to calculate inbreeding coefficients was modified to account for nonzero inbreeding of unknown parents. The modification was done by changing one part of a recursive formula in which the inbreeding of an animal with at least one unknown parent is not zero and replacing it by the mean inbreeding of all animals born the same year. The algorithm is iterative. Testing involved 17million US Holsteins. Convergence was reached in 6 rounds. The computing time per round was 4min, twice as fast as the VanRaden algorithm based on the tabular method. The recursive algorithm is very simple; however, it requires that the recursion takes into account the order of animals. After a simple modification, the algorithm provides a very good approximation of inbreeding when the pedigree is unordered.

Mother-son Parental Care in Horned Larks

Abstract We report the first known observation of mother-son parental care and potential inbreeding in Horned Larks (Eremophila alpestris) near Smithers, British Columbia, Canada. The nest was found with four nestlings and was attended by a female and her son from the previous year. The nestlings appeared healthy, were above average mass, and fledged successfully. The high return rates of adult and juvenile Horned Larks at our study site may have facilitated this social pairing by close relatives. The possibility the son was a helper at the nest is discussed.

Factors Influencing Prereproductive Mortality in the Isolated and Preindustrial Western Mediterranean Population of La Alpujarra, 1900–1950

We study the effects of several variables on the prereproductive mortality pattern in the isolated and rural population of La Alpujarra, located on the western Mediterranean coast (southeast Spain), in the first half of the 20th century. The study is a retrospective analysis from a total sample of 2,200 deliveries, 2,085 of which were born alive and 171 of which did not survive to the 20th birthday. The potential influences of birthdate of children, twinning, firstborn, parental inbreeding, and sex on Alpujarran mortality were analyzed through logistic regression. Parity, family size, and birth interval effects were estimated through the difference between observed and expected mortality rates. In every case four age groups of mortality were considered because of the large influence of child growth: neonatal (less than 1 month of life), postneonatal infant (between 1 month and 1 year old), childhood (1-5 years old), and youth (5-20 years old). The Alpujarran prereproductive mortality pattern can be summarized as the result of three main risk factors: biodemographic, biomechanical, and social and health determinants. In general, every factor showed a decreased effect as children grew. The most significant determinants were birthdate of children, which is more related to increased mother's awareness of child care than to health improvement, and family size associated with decreasing alimentary resources as the sibling number increased. Male mortality was higher than female mortality in children older than 1 year but not for infant mortality, possibly as a result of a reproductive behavior favorable to males. Although firstborn status and twinning appeared associated with high mortality, maternal age and birth interval were related to low risk, but these influences always ceased after the first month of life. Parental inbreeding did not show any effect on infant, childhood, or youth mortality.

Interactive effects of environmental stress and inbreeding on reproductive traits in a wild bird population

1. Conservation biologists are concerned about the interactive effects of environmental stress and inbreeding because such interactions could affect the dynamics and extinction risk of small and isolated populations, but few studies have tested for these interactions in nature. 2. We used data from the long-term population study of song sparrows Melospiza melodia on Mandarte Island to examine the joint effects of inbreeding and environmental stress on four fitness traits that are known to be affected by the inbreeding level of adult birds: hatching success, laying date, male mating success and fledgling survival. 3. We found that inbreeding depression interacted with environmental stress to reduce hatching success in the nests of inbred females during periods of rain. 4. For laying date, we found equivocal support for an interaction between parental inbreeding and environmental stress. In this case, however, inbred females experienced less inbreeding depression in more stressful, cooler years. 5. For two other traits, we found no evidence that the strength of inbreeding depression varied with environmental stress. First, mated males fathered fewer nests per season if inbred or if the ratio of males to females in the population was high, but inbreeding depression did not depend on sex ratio. Second, fledglings survived poorly during rainy periods and if their father was inbred, but the effects of paternal inbreeding and rain did not interact. 6. Thus, even for a single species, interactions between the inbreeding level and environmental stress may not occur in all traits affected by inbreeding depression, and interactions that do occur will not always act synergistically to further decrease fitness.

REPRODUCTIVE PERFORMANCE AS A FUNCTION OF INBREEDING IN PRAIRIE VOLES (MICROTUS OCHROGASTER)

Most studies of inbreeding depression have confounded levels of inbreeding of parents with those of offspring. We used 4 experimental groups of prairie voles (Microtus ochrogaster) in which both parents and offspring were noninbred, parents and offspring were inbred, or parents and offspring differed in their level of inbreeding. For each pair, we recorded latency to the production of the 1st litter, number of litters produced and number of young born in 120 days, litter weights from birth to weaning, and parental behavior. Noninbred parents produced more litters and young and showed shorter interlitter intervals than did inbred parents. Inbred offspring weighed less at birth and weaning. We found no significant differences in parental behaviors among groups. Our results demonstrate that inbreeding depression occurs in prairie voles, and that it may be influenced more by physiological changes in inbred parents or young than by behavioral deficiencies in inbred parents. However, larger sample sizes could reveal that parental behavior does have an effect.

Among- and within-population variation in outcrossing rate of a mixed-mating freshwater snail

Mixed-mating animals self-fertilize a proportion of their offspring. Outcrossing rate may covary with the ecological and historical factors affecting the population. Theory predicts that outcrossing is favored when inbreeding depression is high and when individual heterozygosity is important. Self-fertilization is predicted to be favored when costs of male function, or mate finding are high, for example, when empty patches are colonized by few individuals. In this study, we assessed primary (after hatching) and secondary (after juvenile mortality) outcrossing rates of two mixed-mating snail populations. Our purpose was to assess the variation in mating-system parameters and estimate significance of inbreeding depression for secondary outcrossing rate (the realized outcrossing rate of parents that produce the next generation). Secondary outcrossing rate was higher than the primary outcrossing rate in one of the two populations, suggesting considerable inbreeding depression. In the other study population, secondary outcrossing rates were found to increase when initially low, or decrease when initially high, depending on the family. Moderate outcrossing rates were found to be more stable. Parental inbreeding coefficients were close to zero in both populations. Outcrossing rate was much more variable among families in the population with the lower average outcrossing rate, suggesting that individuals differed considerably in their mating system. Our results add to recent studies suggesting that populations of mixed-mating animals may differ in their mating system parameters and expression of inbreeding depression.

Quantification of Homozygosity in Consanguineous Individuals with Autosomal Recessive Disease

Individuals born of consanguineous union have segments of their genomes that are homozygous as a result of inheriting identical ancestral genomic segments through both parents. One consequence of this is an increased incidence of recessive disease within these sibships. Theoretical calculations predict that 6% (1/16) of the genome of a child of first cousins will be homozygous and that the average homozygous segment will be 20 cM in size. We assessed whether these predictions held true in populations that have preferred consanguineous marriage for many generations. We found that in individuals with a recessive disease whose parents were first cousins, on average, 11% of their genomes were homozygous (n = 38; range 5%-20%), with each individual bearing 20 homozygous segments exceeding 3 cM (n = 38; range of number of homozygous segments 7-32), and that the size of the homozygous segment associated with recessive disease was 26 cM (n = 100; range 5-70 cM). These data imply that prolonged parental inbreeding has led to a background level of homozygosity increased approximately 5% over and above that predicted by simple models of consanguinity. This has important clinical and research implications.

Mating patterns and demography in the tristylous daffodil Narcissus triandrus

Mating patterns in plant populations are influenced by interactions between reproductive traits and ecological conditions, both factors that are likely to vary geographically. Narcissus triandrus, a wide-ranging heterostylous herb, exhibits populations with either two (dimorphic) or three (trimorphic) style morphs and displays substantial geographical variation in demographic attributes and floral morphology. Here, we investigate this variation to determine if demography, morphology, and mating system differ between the two sexual systems. Our surveys in Portugal and NW Spain indicated that dimorphic populations were less dense, of smaller size, and had larger plants and flowers compared to trimorphic populations. Outcrossing rates estimated using allozyme markers revealed similar outcrossing rates in dimorphic and trimorphic populations (t(m) dimorphic=0.759; t(m) trimorphic=0.710). All populations experienced significant inbreeding in progeny (mean F=0.143). In contrast, parental estimates of inbreeding were not significantly different from zero (mean F=0.062), implying that few inbred offspring survive to reproductive maturity due to inbreeding depression. Although the majority of inbreeding results from selfing, significant levels of biparental inbreeding were also detected in eight of the nine populations (mean s(s)-s(m)=0.081). Density was negatively associated with levels of selfing but positively associated with biparental inbreeding. Population size was positively associated with outcrossing but not biparental inbreeding. There were no consistent differences among the style morphs in outcrossing or biparental inbreeding indicating that the maintenance of trimorphism vs dimorphism is unlikely to be associated with inbreeding of maternal parents.