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Background: Clinical observational study demonstrated that hypertension is an independent risk factor for stroke. Furthermore, both hypertension and stroke exhibit genetic predispositions. However, the genetic relationship between hypertension and stroke in first-degree relatives remains unclear., Method: The Genetic effects were validated using an across-Mendelian randomization (MR) approach. The Genome-Wide Association Study summary data used in this study were obtained from a publicly available platform. The primary MR effect employed was inverse-variance weighted (IVW), and the other analysis methods included MR-Egger, weighted median, simple mode, and weighted mode. Prior to MR analysis, tests for MR_PRESSO, pleiotropy, and heterogeneity were conducted., Result: The presence of family history of hypertension significantly contributed to the genetic predisposition to various types of stroke, including ischemic stroke, subarachnoid hemorrhage, lacunar stroke, cardioembolic ischemic stroke, small vessel ischemic stroke, and large artery atherosclerosis-related ischemic stroke., Conclusion: Briefly, hypertension in first-degree relatives has a genetic impact on the risk of stroke development. Shared genetic factors may exist between hypertension and stroke., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: This study aimed to assess the practicality of using a stepwise pedigree-based approach to differentiate between familial and sporadic Dilated Cardiomyopathy (DCM), while also considering timing of the genetic analysis. The analysis includes an examination of the extent to which complete family investigations were conducted in real-world scenarios as well as the length of the investigation., Methods: The stepwise pedigree approach involved conducting a comprehensive family history spanning 3 to 4 generations, reviewing medical records of relatives, and conducting clinical screening using echocardiography and electrocardiogram on first-degree relatives. Familial DCM was diagnosed when at least 2 family members were found to have DCM, and genetic analysis was considered as an option. This study involved a manual review of all DCM investigations conducted at the Centre of Cardiovascular Genetics at Umeå University Hospital, where the stepwise pedigree approach has been employed since 2007., Results: The investigation process had a mean duration of 643 days (95% CI 560.5-724.9). Of the investigations preformed, 94 (68%) were complete, 12 (9%) were ongoing, and 33 (24%) were prematurely terminated and thus incomplete. At the conclusion of the investigations, 55 cases (43%) were classified as familial DCM, 50 (39%) as sporadic DCM, and 22 (18%) remained unassessed due to incomplete pedigrees. Among the familial cases, genetic verification was achieved in 40%., Conclusion: The stepwise pedigree approach is time consuming, and the investigations are often incomplete which may suggest that a more direct approach to genetic analysis, may be warranted.

Boven published, in 1915, his MD thesis at the University of Lausanne in which he examined 60 3- to 4-generation pedigrees ascertained from admitted patients with dementia praecox (DP) and manic-depressive insanity (MDI). He asked three questions: (i) were DP and MDI hereditary? (ii) were they the same or distinct conditions? and (iii) were they Mendelian disorders? Based on the rarity of environmental precipitants severe enough to cause disorder onset and the pattern of disorders in relatives, Boven concluded that both disorders were inherited. He found that MDI largely ran in families through direct transmission across generations while DP was only common in collateral relatives. Both pedigrees contained a substantial number of "psychopathic" (personality disordered) relatives in which DP and MDI pedigrees typically had, respectively, paranoid, and dysthymic/cyclothymic features. Boven concludes that their inheritance is largely distinct but not exclusive, as some pedigrees contained cases of both disorders. With assistance from Wilhelm Weinberg, Boven applied algebraic models with proband correction to rates of DP and MDI in sibships and found the results inconsistent with Mendelian transmission. His study represents among the first examinations, using "modern" methods, of the familial relationship between DP and MDI and the first published in French., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

In the 19th century, psychiatric genetic studies typically utilized a generic category of "insanity." This began to change after 1899, with the publication of Kraepelin's 6th edition containing, among other disorders, his mature concept of dementia praecox (DP). We here review an article published by Ryssia Wolfsohn in 1907 from her dissertation at the University of Zurich entitled "Die Heredität bei Dementia praecox" (The Heredity of Dementia Praecox). This work, performed under the supervision of E. Bleuler, was to our knowledge the first formal genetic study of the then new diagnosis of DP. She investigated 550 DP probands admitted to the Burghölzli hospital with known information about their "heredity burden." For most probands, she had information on parents, siblings, grandparents, and aunts/uncles. Of these patients, only 10% had no psychiatric illness in their families. In the remaining probands, she found rates of the four major categories of psychopathology she investigated: mental illness-56%, nervous disorders-19%, peculiar personalities 12% and alcoholism 13%. Her most novel analyses compared either total familial burden or burden of her four forms of mental disorders on her DP probands divided by subtype and outcome. In neither of these analyses, did she find significant differences., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Introduction: Pelvic girdle pain during and after pregnancy is a major public health problem with significant daily problems for affected women and their families. There is now accumulating evidence that pregnancy-related pelvic girdle pain originates from the sacroiliac joints and the pubic symphysis as well as their extra-articular ligaments. However, the heritability of the disease remains to be determined. We hypothesized that there is an increased familial risk of pregnancy-related pelvic girdle pain., Material and Methods: A population-based national database linkage registry study of approximately 9.3 million individuals within 4.2 million families in Sweden with a recruitment period from 1997 to 2018. The Swedish Multi-generation register was used to find female pairs of twins, full siblings, half-siblings and first cousins where both in the pairs had a completed pregnancy. The outcome measure was diagnosis of pregnancy-related pelvic girdle pain (International Classification of Diseases-10 O26.7 [1997-2018]) in the first pregnancy. Data was obtained from the Swedish Hospital Discharge Register, the Swedish Outpatient Care Register, the Swedish Medical Birth Register, the Primary Healthcare Register, and Medical Treatment Register. Cox regression analysis was used to calculate adjusted estimated effect of the exposure variable familial history of pregnancy-related pelvic girdle pain on the outcome variable pregnancy-related pelvic girdle pain at first birth., Results: From the registers, 1 010 064 women pregnant with their first child within 795 654 families were collected. In total, 109 147 women were diagnosed with pregnancy-related pelvic girdle pain. The adjusted hazard ratio for a familial risk of pregnancy-related pelvic girdle pain was 2.09 (95% CI 1.85-2.37) among twins (monozygotic and dizygotic), 1.78 (95% CI 1.74-1.82) in full siblings, 1.16 (95% CI 1.06-1.28) in half-siblings from the mother, 1.09 (95% CI 1.024-1.16) in half-siblings from the father and 1.09 (95% CI 1.07-1.12) in first cousins., Conclusions: This nationwide observational study showed a familial clustering of pregnancy-related pelvic girdle pain. The hazard ratio for the condition was associated with the degree of relatedness, suggesting that heredity factors contribute to the development of pregnancy-related pelvic girdle pain. There is no causal treatment available for pregnancy-related pelvic girdle pain and further studies are now encouraged to clarify the specific genetic factors that contribute to the disease and for future targeted interventions., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Irma Weinberg, a German-Jewish Neuropsychiatrist/Physician, authored the fourth report from the German Research Institute for Psychiatry in Munich examining the risk for dementia praecox (DP) in particular relatives of DP probands, here first-cousins. She examined 977 cousins of 54 DP probands and found a best-estimate risk of 1.4%. She conducted within-study analyses, showing a much higher risk for DP in the siblings than cousins of DP probands. She studied DP-related personalities showing a familial link between these conditions and risk for DP. She demonstrated that the risk for DP in cousins was impacted substantially by the distribution, in ancestors, of psychosis and personality abnormalities. After completing work on this article, Weinberg worked in private practice in Frankfurt, emigrating to the Netherlands in 1934, where she worked at a Jewish psychiatric hospital. In 1943, German occupiers evacuated the hospital, transporting the patients and staff, either directly to Auschwitz or, like Weinberg, to the Westerbork transit camp. On September 4, 1944, Dr. Weinberg was transported to Theresienstadt and soon thereafter to Auschwitz, where she was murdered at the age of 53. Her history raises painful questions about the relationship between genetic studies of psychiatric illness in prewar Germany and the Holocaust., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Shaw, a British psychiatrist working in India, observed that the incidence of Schizophrenia was higher among a community of Parsis as compared to other ethnic groups. He published his findings in two British journals. The paper drew responses from two other psychiatrists. The debate is examined in colonial context during which occurred and some implications for contemporary research., Competing Interests: Declaration of Competing Interest The Author has no financial conflicts to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most significant obstacles were low predictive power and lack of population diversity in available PRS (selected, respectively, by 53.6% and 29.3% of participants). Nevertheless, 89.8% of participants were optimistic about the use of PRS in the next 10 years, suggesting a belief that current shortcomings could be addressed. Our findings inform about the perceptions of psychiatric professionals regarding PRS and the application of PRS in psychiatry., (© 2023 Wiley Periodicals LLC.)

Since the Modern Synthesis, our ideas of evolution have mostly centered on the information encoded in the DNA molecule and their mechanisms of heredity. Increasing evidence, however, suggests that epigenetic mechanisms have the potential to perpetuate gene activity states in the context of the same DNA sequence. Here, we discuss recent compelling evidence showing that epigenetic signals triggered by environmental stress can persist over very long timeframes, contributing to phenotypic changes in relevant traits upon which selection could act. We argue that epigenetic inheritance plays an important role in fast phenotypic adaptation to fluctuating environments, ensuring the survival of the organisms of a population under environmental stress in the short term while maintaining a "bet-hedging" strategy of reverting to the original state if the environment returns to standard conditions. These examples call for a reevaluation of the role of nongenetic information in adaptive evolution, raising questions about its broader relevance in nature., (© 2023 New York Academy of Sciences.)

A female Lagotto Romagnolo dog with polycystic kidney disease (PKD) and her progeny, including PKD-affected offspring, were studied. All affected dogs appeared clinically inconspicuous, while sonography revealed the presence of renal cysts. The PKD-affected index female was used for breeding and produced two litters with six affected offspring of both sexes and seven unaffected offspring. The pedigrees suggested an autosomal dominant mode of inheritance of the trait. A trio whole genome sequencing analysis of the index female and her unaffected parents identified a de novo heterozygous nonsense variant in the coding region of the PKD1 gene. This variant, NM_001006650.1:c.7195G>T, is predicted to truncate 44% of the open reading frame of the wild-type PKD1 protein, NP_001006651.1:p.(Glu2399*). The finding of a de novo variant in an excellent functional candidate gene strongly suggests that the PKD1 nonsense variant caused the observed phenotype in the affected dogs. Perfect co-segregation of the mutant allele with the PKD phenotype in two litters supports the hypothesized causality. To the best of our knowledge, this is the second description of a PKD1 -related canine form of autosomal dominant PKD that may serve as an animal model for similar hepatorenal fibrocystic disorders in humans.

The establishment, maintenance, and removal of epigenetic modifications provide an additional layer of regulation, beyond genetically encoded factors, by which plants can control developmental processes and adapt to the environment. Epigenetic inheritance, while historically referring to information not encoded in the DNA sequence that is inherited between generations, can also refer to epigenetic modifications that are maintained within an individual but are reset between generations. Both types of epigenetic inheritance occur in plants, and the functions and mechanisms distinguishing the two are of great interest to the field. Here, we discuss examples of epigenetic dynamics and maintenance during selected stages of growth and development and their functional consequences. Epigenetic states are also dynamic in response to stress, with consequences for transposable element regulation. How epigenetic resetting between generations occurs during normal development and in response to stress is an emerging area of research.

Nikolai K. Koltzoff (Koltsov) (1872-1940) is one of the key figures in Russian biology. He essentially initiated Russian physicochemical biology and established a large scientific school in the area. Among his disciples, there are the geneticists B.L. Astaurov, S.S. Chetverikov, N.P. Dubinin, V.P. Efroimson, I.A. Rapoport, V.V. Sakharov, and N.V. Timofeeff-Ressovsky; histologist G.I. Roskin, experimental surgeon A.G. Lapchinsky, developmental biologist M.M. Zavadovsky, physiologist L.V. Krushinsky, microbiologist S.M. Gershenson, biochemist V.A. Engelhardt, hydrobiologist G.G. Vinberg, cytologist M.A. Peshkov, and many other famous Soviet biologists. He made several fundamental discoveries; the first of them was the discovery of the cytoskeleton (1903). He was the first to formulate the idea of a crystal-like mechanism for copying inherited information (1927) and the principles of epigenetics (as well as the term itself, in 1934; it seems astonishing, but as early as 1915, he hypothesized that the gene methylation might be a mechanism of genetic variability). He started the work which later led his disciples V.V. Sakharov and I.A. Rapoport to the discovery of chemical mutagenesis. His research on sex regulation in silkworms was later successfully continued by B.L. Astaurov. Koltzoff encouraged S.S. Chetverikov, the entomologist, to study the genetics of natural Drosophila populations, which went on to form the basis of the Modern Synthesis reconciling Darwinian evolutionary theory and the Mendelian laws of heredity. Unfortunately, the name of N.K. Koltzoff has almost sunk into oblivion. This is largely due to the fact that mentioning his name was prohibited in the USSR over a long period of time, since he was a staunch opponent of Lysenko. In this paper dedicated to the 150th anniversary of Koltzoff, we briefly describe the milestones of the life and scientific research of this outstanding biologist and his scientific school., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

On September 27, 1922, Ernst Rüdin gave an address to the Annual Conference of the German Society of Genetics entitled "Regarding the Heredity of Mental Disturbances." Published in a 37-page article, Rüdin reviewed the progress in the field of Mendelian psychiatric genetics, then hardly more than a decade old. Topics included (a) the status of Mendelian analyses of dementia praecox and manic-depressive insanity which had expanded to include two and three locus and early polygenic models and sometimes included, respectively, schizoid and cyclothymic personalities; (b) a critique of theories for the explanation of co-occurrence of different psychiatric disorders within families; and (c) a sharp methodologic critique of Davenport and Rosanoff's contemporary work which emphasized Rüdin's commitment to careful, expert phenotyping, a primary focus on well-validated psychiatric disorders and not broad spectra of putatively inter-related conditions, and an emphasis on rigorous statistical modeling as seen in his continued collaboration with Wilhelm Weinberg., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Four years before the rediscovery of Mendel's work in 1900, Karl Grassmann published a detailed, scholarly review of the heredity of psychosis which we here review. A full translation is in the appendix. We emphasize seven major conclusions from this review. First, while recognizing the key importance of heredity in the etiology of psychosis. Grassmann was critical of many of the highly speculative extant theories. Second, he reviewed most of the major methodologic concerns in the literature from what kinds of heredity to investigate to the problems with the global use of insanity as a diagnostic category. Third, he discussed in detail genetic theories associated with Degeneration theory, maintaining considerable skepticism. Fourth, he recognized nongenetic contribution to familial transmission. Fifth, he reviewed evidence for both homogeneous and heterogeneous transmission of forms of mental illness in families, suggesting that both were important. Sixth, while he noted that mania, melancholia, and cyclothymia commonly replaced each other in families, Verrücktheit (delusional psychoses) rarely co-segregated in families with these mood disorders. Seventh, Grassmann, like other 19th century writers, saw relatives to be of value only in assessing the level of hereditary predisposition in patients and had limited appreciation of the need for controlled studies., (© 2022 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Heredity has been dismissed as an insignificant object in Claude Bernard's physiology, and the topic is usually ignored by historians. Yet, thirty years ago, Jean Gayon demonstrated that Bernard did elaborate on the subject. The present paper aims at reassessing the issue of heredity in Claude Bernard's project of a "general physiology". My first claim is that Bernard's interest in heredity was linked to his ambitious goal of redefining general physiology in relation to morphology. In 1867, not only was morphology included within experimental physiology, but it also theoretically grounded physiological investigations. By 1878, morphology and physiology were considered as completely independent sciences, and only the latter was perceived as suitable to experimentation. My second claim is that this reversal reflected the existence of two opposite attitudes towards heredity. In the late 1860s, Bernard was convinced that heredity would soon be accessible to experimental manipulation and that new species would be produced in the laboratory exactly like organic chemistry succeeded to do for raw bodies. Ten years later, he ascertained that this was impossible. My third claim is that Bernard was epistemologically ill-equipped to address the issue of heredity. Bernard was strongly committed to a general reasoning scheme that acknowledged only three categories: determining conditions, constant laws and phenomena. This scheme was a key factor in his successes as a physiologist who was able to capture new mechanisms in living bodies. Nonetheless, it also prevented him from understanding how time and history could be endowed with a causal action that cannot be reduced to timeless parameters., (© 2023. Springer Nature Switzerland AG.)

Background: Hypoplastic left heart syndrome (HLHS) is a rare but genetically complex and clinically and anatomically severe form of congenital heart disease (CHD)., Case Presentation: Here, we report on the use of rapid prenatal whole-exome sequencing for the prenatal diagnosis of a severe case of neonatal recurrent HLHS caused by heterozygous compound variants in the MYH6 gene inherited from the (healthy) parents. MYH6 is known to be highly polymorphic; a large number of rare and common variants have variable effects on protein levels. We postulated that two hypomorphic variants led to severe CHD when associated in trans; this was consistent with the autosomal recessive pattern of inheritance. In the literature, dominant transmission of MYH6-related CHD is more frequent and is probably linked to synergistic heterozygosity or the specific combination of a single, pathogenic variant with common MYH6 variants., Conclusions: The present report illustrates the major contribution of whole-exome sequencing (WES) in the characterization of an unusually recurrent fetal disorder and considered the role of WES in the prenatal diagnosis of disorders that do not usually have a genetic etiology., (© 2023. The Author(s).)

Objectives: Schizophrenia is a psychotic disorder with high heritability. There are also indications that an autoimmune-mediated process in the brain underlies development of schizophrenia, and that the insulin receptor A may constitute a main antigen target. Therefore, as the insulin receptor gene hitherto has been little studied in schizophrenia, this study was undertaken to investigate this gene in schizophrenia susceptibility., Materials and Methods: To identify gene variants of possible interest, the whole insulin receptor gene was first DNA-sequenced in all or subgroups of patients with schizophrenia and controls, using the Sanger method and the SOLiD technology. Then, association analyses of total 50 identified gene variants were carried out in the whole study population, consisting of 94 patients and 60 controls., Results: No significant differences in genotype- and allele frequencies for the 50 gene variants were found between all patients and controls. However, in subgroup analyses, rs2229431 and rs747721248 tended to associate with heredity for schizophrenia, rs2229431 associated with height, rs41505247 with body mass index, rs59765738 and rs57476618 with diabetes mellitus (DM) type 1 and/ or heredity for DM type 1, and rs2962, rs2352954, rs2352955 and rs2252673 with DM type 2 and/ or heredity for DM type 2 in patients., Conclusions: In this study, we show associations between heredity, height, body mass index, DM type 1, or DM type 2 and gene variants in the insulin receptor gene in patients with schizophrenia. Taken together, these findings clearly point to that the insulin receptor gene is involved in schizophrenia susceptibility.

Jean-Baptiste Lamarck is well known as a pre-Darwinian proponent of evolution. But much of what has been written on Lamarck, on his 'Lamarckian' belief in the inheritance of acquired characters, and on his conception of the role of the will in biological development mischaracterizes his views. Indeed, surprisingly little in-depth analysis has been published regarding his views on human physiology and development. Further, although since Robert M. Young's signal 1969 essay on Malthus and the evolutionists, Darwin scholars have sought to place Darwin's work in its social and political context, this has yet to be done adequately for Lamarck. Here I address this gap. I argue that the will was of particular importance to Lamarck's social commentary and his hopes for the transformation of the French people and nation. Further, I argue that if we are to really grasp Lamarck's ideas and intentions we need to contextualize his works in relation to prevailing debates in France about the physiology of mind and morals and the future of the nation., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

In recent years, we have seen an increasing amount of evidence pointing to the existence of a non-genetic heredity of the effects of events such as separation from parents, threat to life, or other traumatising experiences such as famine. This heredity is often mediated by epigenetic regulations of gene expression and may be transferred even across several generations. In this review, we focus on studies which involve transgenerational epigenetic inheritance (TEI), with a short detour to intergenerational studies focused on the inheritance of trauma or stressful experiences. The reviewed studies show a plethora of universal changes which stress exposure initiates on multiple levels of organisation ranging from hormonal production and the hypothalamic-pituitary-adrenal (HPA) axis modulation all the way to cognition, behaviour, or propensity to certain psychiatric or metabolic disorders. This review will also provide an overview of relevant methodology and difficulties linked to implementation of epigenetic studies. A better understanding of these processes may help us elucidate the evolutionary pathways which are at work in the course of emergence of the diseases and disorders associated with exposure to trauma, either direct or in a previous generation.

Epigenetics is the field of science that deals with the study of changes in gene function that do not involve changes in DNA sequence and are heritable while epigenetics inheritance is the process of transmission of epigenetic modifications to the next generation. It can be transient, intergenerational, or transgenerational. There are various epigenetic modifications involving mechanisms such as DNA methylation, histone modification, and noncoding RNA expression, all of which are inheritable. In this chapter, we summarize the information on epigenetic inheritance, its mechanism, inheritance studies on various organisms, factors affecting epigenetic modifications and their inheritance, and the role of epigenetic inheritance in the heritability of diseases., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

While heredity is predominantly controlled by what deoxyribonucleic acid (DNA) sequences are passed from parents to their offspring, a small but growing number of traits have been shown to be regulated in part by the non-genetic inheritance of information. Transgenerational epigenetic inheritance is defined as heritable information passed from parents to their offspring without changing the DNA sequence. Work of the past seven decades has transitioned what was previously viewed as rare phenomenology, into well-established paradigms by which numerous traits can be modulated. For the most part, studies in model organisms have correlated transgenerational epigenetic inheritance phenotypes with changes in epigenetic modifications. The next steps for this field will entail transitioning from correlative studies to causal ones. Here, we delineate the major molecules that have been implicated in transgenerational epigenetic inheritance in both mammalian and non-mammalian models, speculate on additional molecules that could be involved, and highlight some of the tools which might help transition this field from correlation to causation., (© 2022 Wiley Periodicals LLC.)

Purpose: The Social Responsiveness Scale (SRS) is frequently used in research settings to measure characteristics associated with autism spectrum disorders (ASD). A short version has been developed but not yet tested for certain properties of the full SRS, such as familiality. The purpose of this study was to determine if prior familiality findings for the full SRS can be replicated using the short form by measuring the associations of the parental Social Responsiveness Scale-Short Form (SRS-SF) scores with child ASD diagnoses and child SRS-SF scores. Methods: We used a nested case-control study within a longitudinal cohort study design. Participants were selected from the Nurses' Health Study II (NHS II). Cases were children of study participants who had been diagnosed with ASD, while controls had not been diagnosed with ASD and were frequency matched by year of birth to cases. 2144 out of 3161 eligible participants returned SRS forms for a child and at least one parent. Participants in NHS II completed SRS forms for their spouses and spouses completed SRS forms for NHS II participants. Parental SRS-SF scores were based on a subset of 16 questions from the SRS. ASD diagnosis among children was reported by the mothers and validated in a subset using the Autism Diagnostic Interview--Revised, as well as child SRS-SF scores. Results: Children whose parents both had elevated SRS-SF scores (those in the top 20% of the study distribution) had a higher odds of ASD diagnosis than those who did not have elevated parental scores (OR 2.25; 95% CI 1.41, 3.58). Additionally, children whose fathers had elevated SRS-SF scores had a higher odds of ASD diagnosis (OR 2.18; 95% CI 1.60, 2.97) than those whose fathers scores were not elevated. In sex-stratified analyses, male children with elevated parental SRS-SF scores had a higher odds of ASD diagnosis than those who did not have elevated parental scores. These associations were not as evident among female children. Parental SRS-SF scores also predicted child SRS-SF scores among controls. Conclusion: These findings are similar to prior findings for the full SRS and support the ability of the SRS-SF to capture familiality of ASD-related traits.

Recent advances in genomics make it possible to predict individual differences in education from polygenic scores that are person-specific aggregates of inherited DNA differences. Here, we systematically reviewed and meta-analyzed the strength of these DNA-based predictions for educational attainment (e.g., years spent in full-time education) and educational achievement (e.g., school grades). For educational attainment (k = 20, n = 16, N[subscript total] = 314,757), a multilevel meta-analysis showed an association with polygenic scores of [rho] = 0.27 (95% CI from 0.22 to 0.32). For educational achievement (k = 19, n = 10, N[subscript total] = 83,788), the association was [rho] = 0.24 (95% CI from 0.18 to 0.30). Eurocentric biases were evident with only 15% of estimates being reported in samples of non-European ancestry. After accounting for sample ancestry, age at assessment, and education measure, the meta-analytic estimates increased to [rho] = 0.29 (95% CI from 0.24 to 0.33) for educational attainment and [rho] = 0.50 (95% CI from 0.39 to 0.61) for educational achievement, indicative of large effect sizes. All meta-analytic estimates were associated with significant heterogeneity. Our findings suggest that DNA-based predictions of education are sizeable but vary across samples and studies. We outline three steps to safeguard potential applications of polygenic score predictions in education to maximize their benefits for personalizing learning, while minimizing the bioethical risks of perpetuating social, cultural, and economic inequalities.

Evolution is the integrative framework of the life sciences. Even though the topic is often not formally introduced before high school, young children already have various ideas about evolutionary principles (variation, inheritance, and selection) and their underlying key concepts (e.g., differential fitness, reproduction, and speciation). Describing and refining those ideas has increasingly received attention over the last two decades. However, we see two scopes of improvement in the field: (1) There is a need to examine children's ideas about evolutionary concepts holistically rather than focusing at specific aspects. (2) Although research has shown that older students have different ideas about animal and plant evolution, there is little data on children's ideas about plant evolution to compare with their ideas about animal evolution. All of this results in an incomplete record of children's pre-existing ideas that would help to design assessments or interventions. Consequently, we developed a set of questions, about the evolutionary principles and interviewed 24 kindergarten children. Most children had basic ideas about individual variation in animals and plants but experienced a lack of knowledge about the origin of variation. Most children seemed to acknowledge plants as living beings and reasoned equally about animals and plants for most concepts. However, many children failed to reason about reproduction and inheritance in plants because they believed plants would not reproduce sexually. Confronted with a selection scenario, most children struggled applying concepts previously shown on an individual level to a population level. Considering our findings, we propose ideas about how to measure and foster children's pre-existing ideas about evolution.

If several relatives died with no will, the order of their deaths could affect the inheritance result. When the order of death is unknown, there are three approaches to determine the inheritance result in this simultaneous death situation: apply an inheritance method that is not affected by the order of death; artificially assign the order of death; stipulate that persons with unknown orders do not inherit each other. The last approach is adopted by the current French Civil Code (denoted as the French Approach). We prove that under some basic requirements, the French Approach is the only valid solution to the order of death problem. Therefore, the inheritance law of a country that does not adopt the French Approach either has unsolvable inheritance problems or violates basic requirements. In the appendix, we study the existence and uniqueness of inheritance methods that are invariant for different orders of death and only violate one requirement, such as gender equality., Competing Interests: The author has declared that no competing interests exist., (Copyright: © 2022 Yue Wang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The universal core of metabolism could have emerged from thermodynamically favoured prebiotic pathways at the origin of life. Starting with H 2 and CO 2 , the synthesis of amino acids and mixed fatty acids, which self-assemble into protocells, is favoured under warm anoxic conditions. Here, we address whether it is possible for protocells to evolve greater metabolic complexity, through positive feedbacks involving nucleotide catalysis. Using mathematical simulations to model metabolic heredity in protocells, based on branch points in protometabolic flux, we show that nucleotide catalysis can indeed promote protocell growth. This outcome only occurs when nucleotides directly catalyse CO 2 fixation. Strong nucleotide catalysis of other pathways (e.g. fatty acids and amino acids) generally unbalances metabolism and slows down protocell growth, and when there is competition between catalytic functions cell growth collapses. Autocatalysis of nucleotide synthesis can promote growth but only if nucleotides also catalyse CO 2 fixation; autocatalysis alone leads to the accumulation of nucleotides at the expense of CO 2 fixation and protocell growth rate. Our findings offer a new framework for the emergence of greater metabolic complexity, in which nucleotides catalyse broad-spectrum processes such as CO 2 fixation, hydrogenation and phosphorylation important to the emergence of genetic heredity at the origin of life.

Fungal cultivation is a defining feature for advanced agriculture in fungus-farming ants and termites. In a third supposedly fungus-farming group, wood-colonizing ambrosia beetles, an experimental proof for the effectiveness of beetle activity for selective promotion of their food fungi over others is lacking and farming has only been assumed based on observations of social and hygienic behaviours. Here, we experimentally removed mothers and their offspring from young nests of the fruit-tree pinhole borer, Xyleborinus saxesenii . By amplicon sequencing of bacterial and fungal communities of nests with and without beetles we could show that beetles are indeed able to actively shift symbiont communities. Although being consumed, the Raffaelea food fungi were more abundant when beetles were present while a weed fungus ( Chaetomium sp.) as well as overall bacterial diversity were reduced in comparison to nests without beetles. Core symbiont communities were generally of low diversity and there were strong signs for vertical transmission not only for the cultivars, but also for secondary symbionts. Our findings verify the existence of active farming, even though the exact mechanisms underlying the selective promotion and/or suppression of symbionts need further investigation.

The extension of biological inheritance beyond gene-centrism is at the center of many debates in evolutionary biology, but it has been relatively ignored in the field of biomedicine. The purpose of this prospective paper is to highlight the potential impact of a new vision of inheritance on medical theory, notably on the concept of hereditary disease. It is also to underline some related practical and social issues., (© 2022 médecine/sciences – Inserm.)

This paper contributes to the ongoing reassessment of the controversy between William Bateson and Karl Pearson by characterising what we call "Batesonian Mendelism" and "Pearsonian biometry" as coherent and competing scientific outlooks. Contrary to the thesis that such a controversy stemmed from diverging theoretical commitments on the nature of heredity and evolution, we argue that Pearson's and Bateson's alternative views on those processes ultimately relied on different appraisals of the methodological value of the statistical apparatus developed by Francis Galton. Accordingly, we contend that Bateson's belief in the primacy of cross-breeding experiments over statistical analysis constituted a minimal methodological unifying condition ensuring the internal coherence of Batesonian Mendelism. Moreover, this same belief implied a view of the study of heredity and evolution as an experimental endeavour and a conception of heredity and evolution as fundamentally discontinuous processes. Similarly, we identify a minimal methodological unifying condition for Pearsonian biometry, which we characterise as the view that experimental methods had to be subordinate to statistical analysis, according to methodological standards set by biometrical research. This other methodological commitment entailed conceiving the study of heredity and evolution as subsumable under biometry and primed Pearson to regard discontinuous hereditary and evolutionary processes as exceptions to a statistical norm. Finally, we conclude that Batesonian Mendelism and Pearsonian biometry represented two potential versions of a single genetics-based evolutionary synthesis since the methodological principles and the phenomena that played a central role in the former were also acknowledged by the latter-albeit as fringe cases-and conversely., (© 2022. Springer Nature Switzerland AG.)

An understanding of genetics is becoming increasingly relevant to receiving medical care. It is important for health care providers and educators, including genetic counselors, to understand patients' perceptions about trait transmission and their interpretation of terms used in biomedicine. Knowledge about the patient perspective about trait transmission is important when health care providers are not fluent in the patient's language. Sixty Latinx immigrant adults (30 men and 30 women) who were born in Mexico or Central America (MCA) and living in North Carolina were interviewed about their heredity beliefs. By design, most participants had limited education. Eight percent had a least a high school education; 45% had less than a seventh grade education. Semi-structured, in-depth interviews were conducted to examine how participants think and discuss trait transmission. The translated transcripts were systematically analyzed using a case-based approach, supplemented by theme-based coding. Five lay mental models of heredity were identified that varied in terms of involvement of genes. Four of the five heredity mental models encompass genes; four out of five mental models do not link DNA to heredity. The centrality of blood, whether used metaphorically or literally, varies widely across the models. One model references God and depicts that heredity involves blood and/or genes, but not DNA. The mental models of heredity for most adult immigrants with limited education do not include DNA. Trait transmission by blood appears to have a more prominent role in lay mental models held by Mexicans than Central Americans. Increased patient knowledge about genetics can facilitate shared decision-making as genetics becomes increasingly relevant to medical care. Efforts to educate people can be most effective when we first understand the layperson's conceptions or mental models. Health care providers and educators should be aware that MCA adults with limited formal education hold diverse mental models about heredity., (© 2022 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

The upheavals of late eighteenth century Europe encouraged people to demand greater liberties, including the freedom to explore the natural world, individually or as part of investigative associations. The Moravian Agricultural and Natural Science Society, organized by Christian Carl André, was one such group of keen practitioners of theoretical and applied scientific disciplines. Headquartered in the "Moravian Manchester" Brünn (nowadays Brno), the centre of the textile industry, society members debated the improvement of sheep wool to fulfil the needs of the Habsburg armies fighting in the Napoleonic Wars. Wool, as the raw material of soldiers' clothing, could influence the war's outcome. During the early nineteenth century, wool united politics, economics, and science in Brno, where breeders and natural scientists investigated the possibilities of increasing wool production. They regularly discussed how "climate" or "seed" characteristics influenced wool quality and quantity. Breeders and academics put their knowledge into immediate practice to create sheep with better wool traits through consanguineous matching of animals and artificial selection. This apparent disregard for the incest taboo, however, was viewed as violating natural laws and cultural norms. The debate intensified between 1817 and 1820, when a Hungarian veteran soldier, sheep breeder, and self-taught natural scientist, Imre (Emmerich) Festetics, displayed his inbred Mimush sheep, which yielded wool extremely well suited for the fabrication of light but strong garments. Members of the Society questioned whether such "bastard sheep" would be prone to climatic degeneration, should be regarded as freaks of nature, or could be explained by natural laws. The exploration of inbreeding in sheep began to be distilled into hereditary principles that culminated in 1819 with Festetics's "laws of organic functions" and "genetic laws of nature," four decades before Gregor Johann Mendel's seminal work on heredity in peas., (© 2022. The Author(s).)

Early in the 20th century Bateson, Doncaster and Punnett formed a cooperative collective to share research findings on the chromosome theory of heredity (CTH). They cross-bred plants and animals to correlate behaviour of chromosomes and heredity of individual traits. Doncaster was the most enthusiastic proponent of the new theory and worked for years to convince Bateson and Punnett on its relevance to their own research. The two younger biologists collaborated with Bateson, the preeminent geneticist in England. As their own reputations developed, their research findings allied with the consensus on the importance of the CTH by the broader scientific community. After Doncaster's tragic death in 1920, major objections to the theory had been resolved; Bateson and Punnett then utilized the CTH to construct chromosome maps detailing locations of specific genes on particular chromosomes in several different species. The marriage of heredity and cytology enhanced confidence that the theory was an accurate mechanism to explain inheritance in both plants and animals.

New Findings: What is the topic of this review? Revisiting the 2013 article 'Physiology is rocking the foundations of evolutionary biology'. What advances does it highlight? The discovery that the genome is not isolated from the soma and the environment, and that there is no barrier preventing somatic characteristics being transmitted to the germline, means that Darwin's pangenetic ideas become relevant again., Abstract: Charles Darwin spent the last decade of his life collaborating with physiologists in search of the biological processes of evolution. He viewed physiology as the way forward in answering fundamental questions about inheritance, acquired characteristics, and the mechanisms by which organisms could achieve their ends and survival. He collaborated with 19th century physiologists, notably John Burdon-Sanderson and George Romanes, in his search for the mechanisms of transgenerational inheritance. The discovery that the genome is not isolated from the soma and the environment, and that there is no barrier preventing somatic characteristics being transmitted to the germline, means that Darwin's pangenetic ideas become relevant again. It is time for 21st century physiology to come to the rescue of evolutionary biology. This article outlines research lines by which this could be achieved., (© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Complex kinship analysis is a critical issue in forensic genetics. To address this issue, 55 STRs and 94 SNPs collected from four commercial forensic typing kits [three kits were based on a capillary electrophoresis (CE) platform and one was based on a next-generation sequencing (NGS) platform] were employed to test the system power for 2nd-degree and 3rd-degree kinship analysis. To measure the kinship index in related individuals, likelihood ratios (LRs) were calculated based on length and sequence polymorphism information (LR length and LR sequence , respectively) from simulation as well as true pedigree samples. LRs calculated based on sequence information are generally higher than those based on length information. The sensitivity, specificity, and effectiveness to distinguish the 2nd- and 3rd-degree kinship were estimated from four marker sets with different numbers of markers. As expected, system power for kinship analysis improved by increasing the number of markers and using LR sequence , instead of LR length . Furthermore, the system power based on 55 STRs from the CE platform is equal to the 40 STRs and 94 SNPs from one CE kit and the kit based on NGS platform for both 2nd-degree and 3rd-degree kinship analysis. For discrimination of 2nd-degree kinship, the system effectiveness is 86.63% with an error ratio < 0.01 using the 55 STRs from the CE platform. Using sequence information from the 55 STRs and 94 SNPs, the system effectiveness is 94.43%, with an error ratio < 0.001 for 2nd-degree kinship analysis and 64.34% with an error ratio < 0.05 for 3rd-degree kinship analysis, indicating that these markers are powerful for 2nd-degree kinship analysis and can be used for 3rd-degree kinship analysis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Clustering of vision threatening diabetic retinopathy within specific families can be the result of similarities in life style but may also be due to a common genetic background. An evaluation of the role of heredity for the development of diabetic retinopathy may help adjusting control intervals in screening program to each patient's individual risk profile. Methods: Survival analysis was used to study whether family history of diabetes among men and women with type 1 or type 2 diabetes together with the degree of heredity could be added as risk factors to improve the prediction of the risk for developing proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). The study was conducted on data from 12,281 patients followed in the Aarhus area, Denmark, from 1 January 2003 to 1 July 2019. Results: The risk for developing PDR was significantly reduced 2-11 years after known onset of diabetes in the presence of female family members with type 1 diabetes, and the risk for developing DME significantly increased 4-24 years after onset of diabetes in the presence of family members with type 2 diabetes of any sex. These hereditary factors were independent of other studied risk factors such as previous cataract surgery, age of onset of diabetes, metabolic regulation and blood pressure. Conclusions: The presence of family members with diabetes affects the risk for developing vision threatening diabetic retinopathy and affects the risk for developing PDR and DME differently. This evidence may help individualizing the control intervals in screening programmes for diabetic retinopathy.

One claim found in the received historiography of the biometrical school (comprised primarily of Francis Galton, Karl Pearson, and W. F. R. Weldon) is that one of the biometricians' great flaws was their inability to look past their population-focused, statistical, gradualist understanding of evolutionary change - which led, in part, to their ignoring developments in cellular biology around 1900. I will argue, on the contrary, that the work of the biometricians was, from its earliest days, fundamentally concerned with connections between statistical patterns of inheritance and the underlying cellular features that gave rise to them. Such work remained current with contemporary knowledge of chromosomes, cytology, and development; in this article, I explore the first case. The biometricians were thus well positioned to understand the relationship between the patterns of Mendelian inheritance and the statistical distributions with which they primarily occupied themselves. Ignorance of this connection, then, is not the reason why they rejected Mendelism. Further, both Galton and Weldon - though each in their own unique way - decided to turn to biological detail as a way to better justify the generality of their statistical approaches to heredity. Perhaps paradoxically, then, for these biometricians, detail offered an approach to theoretical generality., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Recent investigations with non-model species and whole-genome approaches have challenged several paradigms in animal epigenetics. They revealed that epigenetic variation in populations is not the mere consequence of genetic variation, but is a semi-independent or independent source of phenotypic variation, depending on mode of reproduction. DNA methylation is not positively correlated with genome size and phylogenetic position as earlier believed, but has evolved differently between and within higher taxa. Epigenetic marks are usually not completely erased in the zygote and germ cells as generalized from mouse, but often persist and can be transgenerationally inherited, making them evolutionarily relevant. Gene body methylation and promoter methylation are similar in vertebrates and invertebrates with well methylated genomes but transposon silencing through methylation is variable. The new data also suggest that animals use epigenetic mechanisms to cope with rapid environmental changes and to adapt to new environments. The main benefiters are asexual populations, invaders, sessile taxa and long-lived species., (© 2022 The Authors. BioEssays published by Wiley Periodicals LLC.)

This article explores the collaborative research of the Nobel laureate Hans Spemann (1869-1941) and the Swiss zoologist Fritz Baltzer (1884-1974) on problems at the intersection of development and heredity and raises more general questions concerning science and politics in Germany in the interwar period. It argues that Spemann and Baltzer's collaborative work made a significant contribution to the then ongoing debates about the relation between developmental physiology and hereditary studies, although Spemann distanced himself from Drosophila genetics because of his anti-reductionist position. The article analyzes how Spemann framed the issues of heredity in terms of an epigenetic principle in the context of his work on the "organizer," and it explores the experimental dynamics of research on newt merogones carried out by Baltzer in a methodological development of Spemann's constriction experiments. Finally, these research attempts are discussed as part of a broader "prehistory" of the mid-twentieth century cell nuclear transplantation experiments, which provided the basis for later animal cloning., (© 2022. The Author(s).)

Recent evidence suggests that a polyaneuploid cancer cell (PACC) state may play a key role in the adaptation of cancer cells to stressful environments and in promoting therapeutic resistance. The PACC state allows cancer cells to pause cell division and to avoid DNA damage and programmed cell death. Transition to the PACC state may also lead to an increase in the cancer cell's ability to generate heritable variation (evolvability). One way this can occur is through evolutionary triage. Under this framework, cells gradually gain resistance by scaling hills on a fitness landscape through a process of mutation and selection. Another way this can happen is through self-genetic modification whereby cells in the PACC state find a viable solution to the stressor and then undergo depolyploidization, passing it on to their heritably resistant progeny. Here, we develop a stochastic model to simulate both of these evolutionary frameworks. We examine the impact of treatment dosage and extent of self-genetic modification on eco-evolutionary dynamics of cancer cells with aneuploid and PACC states. We find that under low doses of therapy, evolutionary triage performs better whereas under high doses of therapy, self-genetic modification is favored. This study generates predictions for teasing apart these biological hypotheses, examines the implications of each in the context of cancer, and provides a modeling framework to compare Mendelian and non-traditional forms of inheritance., (© 2022. The Author(s).)

Gregor Mendel was an Augustinian priest in the Monastery of St. Thomas in Brünn (Brno, Czech Republic) as well as a civilian employee who taught natural history and physics in the Brünn Modern School. The monastery's secular function was to provide teachers for the public schools across Moravia. It was a cultural, educational, and artistic center with an elite core of friar-teachers with a well-stocked library and other amenities including a gourmet kitchen. It was wealthy, with far-flung holdings yielding income from agricultural productions. Mendel had failed his tryout as a parish priest and did not complete his examination for teaching certification despite 2 y of study at the University of Vienna. In addition to his teaching and religious obligations, Mendel carried out daily meteorological and astronomical observations, cared for the monastery's fruit orchard and beehives, and tended plants in the greenhouse and small outdoor gardens. In the years 1856 to 1863, he carried out experiments on heredity of traits in garden peas regarded as revolutionary today but not widely recognized during his lifetime and until 16 y after his death. In 1868 he was elected abbot of the monastery, a significantly elevated position in the ecclesiastical and civil hierarchy. While he had hoped to be elected, and was honored to accept, he severely underestimated its administrative responsibilities and gradually had to abandon his scientific interests. The last decade of his life was marred by an ugly dispute with civil authorities over monastery taxation.

When Mendel's work was rediscovered in 1900, and extended to establish classical genetics, it was initially seen in opposition to Darwin's theory of evolution by natural selection on continuous variation, as represented by the biometric research program that was the foundation of quantitative genetics. As Fisher, Haldane, and Wright established a century ago, Mendelian inheritance is exactly what is needed for natural selection to work efficiently. Yet, the synthesis remains unfinished. We do not understand why sexual reproduction and a fair meiosis predominate in eukaryotes, or how far these are responsible for their diversity and complexity. Moreover, although quantitative geneticists have long known that adaptive variation is highly polygenic, and that this is essential for efficient selection, this is only now becoming appreciated by molecular biologists-and we still do not have a good framework for understanding polygenic variation or diffuse function.

Among the so-called sheep breeders interested in biological inheritance in the late eighteenth and early nineteenth centuries and well before Gregor Johann Mendel, J. M. Ehrenfels (1767-1843) produced some of the most cogent writings on the subject. Although earlier in his career Ehrenfels was a strong advocate of environmental factors as influencers on the appearance of organisms, as a result of his discussions with Imre Festetics, he became convinced that whatever is passed from parents to progeny is more important and it is dependent on a "genetic force, the mother of all living things". The sheep breeders kept issues of inheritance at the forefront of the Central European cultural context late into the nineteenth century.

In science, certain theories led to a paradigm shift in human being's approach to explain nature, such as the theory of relativity, the quantum theory, and the theory of evolution. The latter explains the emergence of biodiversity on Earth and all living beings' relatedness, including humans. Accordingly, evolutionary theory is a central part of scientific literacy. However, scholars have demonstrated that misconceptions emerging in childhood hinder learners from grasping evolutionary processes. Implementing evolution in early science education could enhance scientific ideas as a basis for subsequent learning at school. Currently, children's literature that deals with evolution is increasing and may enable more children to encounter evolutionary theory before entering school. This explorative study aimed to analyze how children's books about evolution approach explaining this complex topic to young children in terms of covered contents, underlying concepts and use of language. We conducted (1) a text-based qualitative content analysis of 31 children's books in the categories of organismal context, evolutionary principles, and misconceptions, and (2) a computer-supported content analysis of 33 word labels concerning (a) scientific terms and (b) verbs expressing evolutionary change. Although evolution is a universal concept, children's books seem to promote specific contexts such as animal and human evolution. Even though the principle of selection requires an understanding of complex interactions between individuals and environmental factors, this principle was more frequent than the principles variation and inheritance. Phylogenetic history was covered more often than basic evolutionary processes, and evolutionary change was mainly mentioned at the species level over long periods. Besides, most books conveyed misconceptions such as transformationist, teleological or anthropomorphic reasoning. Consequently, books covering evolution may bias children's first ideas concerning this topic or introduce unscientific ideas. Based on our results, we propose implications for early evolution educators and education researchers., Competing Interests: The authors have declared that no competing interests exist.

Gregor Mendel is widely recognised as the founder of genetics. His experiments led him to devise an enduring theory, often distilled into what are now known as the principles of segregation and independent assortment. Although he clearly articulated these principles, his theory is considerably richer, encompassing the nature of fertilisation, the role of hybridisation in evolution, and aspects often considered as exceptions or extensions, such as pleiotropy, incomplete dominance, and epistasis. In an admirable attempt to formulate a more expansive theory, he researched hybridisation in at least twenty plant genera, intentionally choosing some species whose inheritance he knew would deviate from the patterns he observed in the garden pea (Pisum sativum). Regrettably, he published the results of only a few of these additional experiments; evidence of them is largely confined to letters he wrote to Carl von Nägeli. Because most original documentation is lost or destroyed, scholars have attempted to reconstruct his history and achievements from fragmentary evidence, a situation that has led to unfortunate omissions, errors, and speculations. These range from historical uncertainties, such as what motivated his experiments, to unfounded suppositions regarding his discoveries, including assertions that he never articulated the principles ascribed to him, staunchly opposed Darwinism, fictitiously recounted experiments, and falsified data to better accord with his theory. In this review, I have integrated historical and scientific evidence within a biographical framework to dispel misconceptions and provide a clearer and more complete view of who Mendel was and what he accomplished., (© 2022. The Author(s), under exclusive licence to The Genetics Society.)