Sheep litter size heredity basis using genome-wide selective analysis.

Sheep are important herbivorous domestic animal globally, and the Chinese indigenous sheep breed has a multitude of economically significant variations due to the diverse geographical and ecological conditions. In particular, certain native breeds exhibit a visible high litter size phenotype due to the selection pressure of natural and artificial for thousands of years, offering an ideal animal model for investigating sheep's fecundity. In this study, selective signal analysis was performed on public whole-genome sequencing data from 60 sheep across eight breeds to identify candidate genes related to litter size. Results revealed that a total of 34,065,017 single-nucleotide polymorphisms (SNPs) were identified from all sheep, and 65 candidate genes (CDGs) were pinpointed from the top 1% of interacted windows and SNPs between the pairwise fixation index (FST, >0.149543) and cross-population extended haplotype homozygosity (XP-EHH, >0.701551). A total of 41 CDGs (e.g. VRTN, EYA2 and MCPH1) were annotated to 576 GO terms, of which seven terms were directly linked to follicular and embryonic development (e.g. TBXT, BMPR1B, and BMP2). In addition, 73 KEGG pathways were enriched by 21 CDGs (e.g. ENTPD5, ABCD4 and RXFP2), mainly related to Hippo (TCF4, BMPR1B and BMP2), TGF-ß (BMPR1B and BMP2), PI3K-Akt (ITGB4, IL4R and PPP2R5A) and Jak-STAT signalling pathways (IL20RA and IL4R). Notably, a series of CDGs was under strong selection in sheep with high litter size traits. These findings result could improve the comprehension of the genetic underpinnings of sheep litter size. Furthermore, it provides valuable CDGS for future molecular breeding.

Genetic analysis and family screening for dilated cardiomyopathy: a retrospective analysis of the stepwise pedigree approach.

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.

[The hereditary vessel disease CADASIL].

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease of the brain characterized by progressive white matter lesions, subcortical infarcts, and cognitive decline. This autosomal dominant disorder is caused by mutations in the NOTCH3 gene located on chromosome 19, resulting in the accumulation of granular osmiophilic material within the walls of small arteries and arterioles. Clinically, CADASIL typically manifests in mid-adulthood with recurrent ischemic events, migraine with aura, mood disturbances, and cognitive impairment. Neuroimaging plays a crucial role in the diagnosis of CADASIL, with characteristic findings including white matter hyperintensities particularly in the anterior temporal lobe and external capsule.

Clarifying Mendelian vs non-Mendelian inheritance.

Gregor Mendel developed the principles of segregation and independent assortment in the mid-1800s based on his detailed analysis of several traits in pea plants. Those principles, now called Mendel's laws, in fact, explain the behavior of genes and alleles during meiosis and are now understood to underlie "Mendelian inheritance" of a wide range of traits and diseases across organisms. When asked to give examples of inheritance that do NOT follow Mendel's laws, in other words, examples of non-Mendelian inheritance, students sometimes list incomplete dominance, codominance, multiple alleles, sex-linked traits, and multigene traits and cite as their sources the Khan Academy, Wikipedia, and other online sites. Against this background, the goals of this Perspective are to (1) explain to students, healthcare workers, and other stakeholders why the examples above, in fact, display Mendelian inheritance, as they obey Mendel's laws of segregation and independent assortment, even though they do not produce classic Mendelian phenotypic ratios and (2) urge individuals with an intimate knowledge of genetic principles to monitor the accuracy of learning resources and work with us and those resources to correct information that is misleading.

Whole-exome sequencing revealed a likely pathogenic variant in NF1 causing neurofibromatosis type I and Arrhythmogenic Cardiomyopathy.

BACKGROUND: Neurofibromatosis type I (NF1) is a genetic disorder characterized by the tumor's development in nerve tissue. Complications of NF1 can include pigmented lesions, skin neurofibromas, and heart problems such as cardiomyopathy. In this study, we performed whole-exome sequencing (WES) on an Iranian patient with NF1 to identify the genetic cause of the disease. METHODS: Following clinical assessment, WES was used to identify genetic variants in a family with a son suffering from NF1. No symptomatic manifestations were observed in other family members. In the studied family, in silico and segregation analysis were applied to survey candidate variants. RESULTS: Clinical manifestations were consistent with arrhythmogenic cardiomyopathy (ACM). WES detected a likely pathogenic heterozygous missense variant, c.3277G > A:p.Val1093Met, in the NF1 gene, confirmed by PCR and Sanger sequencing. The patient's parents and brother had a normal sequence at this locus. CONCLUSIONS: Although there is no cure for NF1, genetic tests, such as WES, can detect at-risk asymptomatic family members. Furthermore, cardiac evaluation could also help these patients before heart disease development.

A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Genetic correlations between liver fat content, metabolic health, and adiposity distribution in the Fels Longitudinal Study.

BACKGROUND AND AIMS: Hepatic steatosis is known to be heritable, but its genetic basis is mostly uncharacterized. Steatosis is associated with metabolic and adiposity features; recent studies hypothesize that shared genetic effects between these traits could account for some of the unexplained heritability. This study aimed to quantify these genetic associations in a family-based sample of non-Hispanic white adults. METHODS AND RESULTS: 704 participants (18-95 years, 55.8% female) from the Fels Longitudinal Study with an MRI assessment of liver fat were included. Quantitative genetic analyses estimated the age- and sex-adjusted heritability of individual traits and the genetic correlations within trait pairs. Mean liver fat was 5.95% (SE = 0.23) and steatosis (liver fat >5.56%) was present in 29.8% of participants. Heritability (h2± SE) of steatosis was 0.72 ± 0.17 (p = 6.80e-6). All other traits including liver enzymes, fasting glucose, HOMA-IR, visceral and subcutaneous adipose tissue (VAT, SAT), body mass index, body fat percent, waist circumference, lipids and blood pressure were also heritable. Significant genetic correlations were found between liver fat and all traits except aspartate aminotransferase (AST), and among most trait pairs. Highest genetic correlations were between liver fat and HOMA-IR (0.85 ± 0.08, p = 1.73e-8), fasting glucose and ALT (0.89 ± 0.26, p = 6.68e-5), and HOMA-IR with: waist circumference (0.81 ± 0.12, p = 3.76e-6), body fat percent (0.78 ± 0.12 p = 2.42e-5) and VAT (0.73 ± 0.07, p = 6.37e-8). CONCLUSIONS: Common genes may exist between liver fat accumulation, metabolic features and adiposity phenotypes.

"At a Glance:" The Role of Diagrammatic Representations in Eugenics Appropriations of the "Infamous Juke Family".

The case of the Juke family is one of the most notable episodes of the history of eugenics in the USA. The Jukes were initially brought to the fore in the 1870s by a famous investigation that aimed at estimating the interplay of heredity and environment in determining the problems of poverty and crime. This inquiry triggered a harsh confrontation between two polar interpretations of the study, an "environmentalist" one and a "hereditarian" one. It was with the later reassessment of the case made by the Eugenics American Office (ERO) in the 1910s that the controversy was considered closed with the victory of the eugenicists' hereditarian stance. As a result, the family was made a living proof of the alleged hereditary nature of crime and pauperism and a case study in support of the eugenicists' plea for the sterilization of people deemed the bearers of hereditary defectiveness. In this article, I explore the role played by pedigrees and other diagrammatic representations in the eugenicists' appropriation of the meaning of the case of the Juke family and the role played by this appropriation in asserting the superiority of the ERO's method of work over rival approaches.

A Novel Mutation (Lys31Arg) in the DMD Gene Impacts on Neuromuscular Dysfunctions Found by Whole Exome Sequencing and In Silico Analyses in an Iranian Family.

BACKGROUND: Duchene Muscular Disorder (DMD) is a severe X-linked recessive neuromuscular disease. Previous reports predicted that one-third of cases with a fatal X-linked recessive disease will be caused by a novel mutation, and the mutation rate for DMD seems to be higher in males. OBJECTIVE: A novel mutation in the DMD gene DMD (NM_004006.3):c.92A>G (p.Lys31Arg) is suggested for males because of their heterozygous mothers carrying the mutant alleles. METHOD: Whole Exome Sequencing (WES) was done for a 25-year-old female followed by the screening of the novel mutation in her parents and her brother by the Sanger sequencing technique. Some in silico analyses were run to find the putative alterations in wild-type and mutant structures by PolyPhen-2 and Mupro. Notably, SWISS-MODEL was performed to build a reliable model for the mutant allele based on the PDB ID: 1DXX structure. Also, superimposition was done by PyMol. RESULTS: WES analysis revealed three novel mutations including DLD (exon13:c.G1382A:p. G461E), ABCA3 (exon12:c.G1404C:p.W468C), and DMD (exon2:c.A92G:p.K31R) in the case. Focusing on DMD mutation, Sanger sequencing of the patient's parents and brother indicated no mutant allele in her mother and brother but a mutant allele in her father as a hemizygous pattern. In silico analyses showed no considerable change regarding pathogenic impact. CONCLUSION: In conclusion, our findings revealed no pathogenic effect of the new mutation (K31R) of the DMD gene in an Iranian 25-year-old woman. Because of the DMD importance in preclinical diagnosis, these data may shed a light on the diagnosis of this mutation in future pregnancies.

Ryssia Wolfsohn's 1907 dissertation on "the heredity of dementia praecox".

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.

William Boven's 1915 thesis "Similarity and Mendelism in the heredity of dementia praecox and manic-depressive insanity".

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.

Representações sociais sobre maternidade na reprodução humana assistida: discursos de mulheres inférteis / Social representations of motherhood in assisted human reproduction: discourses of infertile women / Representaciones sociales de la maternidad en la reproducción humana asistida: relatos de mujeres infértiles

Este trabalho tem o objetivo de analisar as concepções de maternidade para mulheres inférteis de diferentes níveis socioeconômicos que estão em tratamento de reprodução assistida. Trata-se de um estudo qualitativo, descritivo, que utilizou como instrumento uma entrevista semiestruturada e contemplou temas como o significado de família, desejo/expectativas sobre filho e gestação e expectativas sobre a maternidade. Participaram da pesquisa 48 mulheres inférteis acima de 35 anos que usam tecnologias de reprodução assistida de alta complexidade em instituições privada e pública. Os dados foram tratados pela análise de conteúdo em que emergiram os temas: representações sociais da família; representações sociais da maternidade; expectativas com a gestação e os modelos maternos; e o filho imaginado. As participantes representaram a família de forma positiva, como um sistema de suporte, de fundação e origem de amor, configurando-a como um laço social. Por outro lado, as concepções de família com base na consanguinidade também estiveram presentes, representando a família pela perpetuação da espécie e pela importância do laço biológico. A maternidade foi marcada por significativa idealização, sendo vista como um papel gratificante e de realização da feminilidade. O peso da cobrança social para procriar também foi sentido como um dever a cumprir e que, na impossibilidade de se realizar, gera sentimentos de inferioridade, menos-valia, impotência e inadequação perante a sociedade, o que reforça o estigma da infertilidade. Tais resultados apontam a importância de reflexões sobre o papel da mulher na nossa cultura, visto que a maternidade é ainda utilizada como medida para o sucesso ou fracasso feminino. Faz-se necessário também refletir sobre a possibilidade da maior inserção do trabalho psicológico na reprodução assistida, visto a carga emocional e social envolvidas nesse processo.(AU)

This study aimed to analyze the conceptions of motherhood for infertile women from different socioeconomic levels who are undergoing assisted reproduction treatment. This is a qualitative and descriptive study that used a semi-structured interview as an instrument and included topics such as the meaning of family and desires/expectations about the child, pregnancy, and motherhood. A total of 48 infertile women over 35 years of ages using high-complexity assisted reproductive technologies in private and public institutions participated in this research. The data were treated by content analysis in which the following themes emerged: family social representations; social representations of motherhood; expectations with pregnancy and maternal models; and the imagined son. Participants represented the family in a positive way as a support system and the foundation and origin of love, embracing the family as a social bond. On the other hand, the family concepts based on inbreeding were also present, representing the family by perpetuation of the species and the importance of biological bonds. Motherhood was marked by significant idealization, being seen as a gratifying role and the fulfillment of femininity. The weight of the social demand to procreate was also felt as a duty to be fulfilled that, in the impossibility of carrying it out, generates feelings of inferiority, worthlessness, impotence, and inadequacy toward society, which reinforce the stigma of infertility. Results point to the necessary reflections on the role of women and our culture since Motherhood is still used as a measure of female success or failure. They also point to a reflection on the possibility of greater inclusion of psychological work in assisted reproduction given the emotional and social burden involved in this process.(AU)

Este estudio tuvo como objetivo analizar las concepciones de maternidad de mujeres infértiles, de diferentes niveles socioeconómicos, que se encuentran en tratamiento de reproducción asistida. Se trata de un estudio cualitativo, descriptivo, que utilizó como instrumento una entrevista semiestructurada e incluyó temas como el sentido de la familia, deseos/expectativas sobre el hijo y el embarazo y expectativas sobre la maternidad. Participaron en la investigación un total de 48 mujeres infértiles, mayores de 35 años, usuarias de tecnologías de reproducción asistida de alta complejidad en instituciones públicas y privadas. Los datos se sometieron a análisis de contenido del cual surgieron los temas: representaciones sociales familiares; representaciones sociales de la maternidad; expectativas con el embarazo y modelos maternos; hijo imaginado. Las participantes representaron a la familia de manera positiva, como sistema de apoyo, fundamento y origen del amor, configurándola como vínculo social. Por otro lado, también estuvieron presentes las concepciones familiares basadas en la consanguinidad, representando a la familia para la perpetuación de la especie y la importancia del vínculo biológico. La maternidad estuvo marcada por una importante idealización, vista como un rol gratificante y de realización de la feminidad. También se sintió el peso de la demanda social de procrear como un deber que cumplir y que, ante la imposibilidad de realizarlo, genera sentimientos de inferioridad, desvalorización, impotencia e inadecuación en la sociedad, lo que refuerza el estigma de la infertilidad. Por tanto, son necesarias reflexiones sobre el papel de la mujer en nuestra cultura, ya que la maternidad se sigue utilizando como medida del éxito o fracaso femenino. También se reflexiona sobre la posibilidad de una mayor inclusión del trabajo psicológico en la reproducción asistida dada la carga emocional y social que implica este proceso.(AU)

Significados atribuídos por mulheres com câncer de mama ao grupo de apoio / Meanings attributed by women with breast cancer to a support group / Significados atribuidos por las mujeres con cáncer de mama al grupo de apoyo

A sobrevivência ao câncer de mama é um problema de saúde pública que demanda serviços especializados com foco na reabilitação psicossocial. Entre as necessidades identificadas nesse contexto está o incentivo à adoção de estratégias de promoção de autocuidados pelas mulheres. Uma das estratégias adotadas consiste no grupo de apoio psicológico, que auxilia as pacientes a enfrentar a longa jornada do tratamento. Assim, o objetivo deste estudo é compreender os significados produzidos por mulheres com câncer de mama sobre sua participação em um grupo de apoio. Trata-se de um estudo qualitativo, descritivo e exploratório realizado com dez mulheres com câncer de mama usuárias de um serviço de reabilitação para mastectomizadas. Como referencial metodológico foi utilizada a Teoria Fundamentada nos Dados. A coleta de dados foi realizada por meio de entrevista aberta em profundidade e os conteúdos foram transcritos e codificados. A análise indutiva e o método de comparação constante foram aplicados nos processos de codificação aberta, axial e seletiva, que permitiram identificar três categorias nucleares: percepção das atividades realizadas no grupo, identificação de benefícios e barreiras do convívio no grupo e transformações decorrentes da participação. As participantes significaram sua presença no grupo como fonte de acolhimento, apoio, desenvolvimento de recursos pessoais e amizades, contribuindo para promover sua qualidade de sobrevida. Além dos potenciais benefícios, também foram identificadas barreiras que podem dificultar a adesão e continuidade da participação no grupo, o que sugere a necessidade de incorporar no cuidado um olhar para as dimensões subjetivas da saúde da mulher.(AU)

Surviving breast cancer is a public health problem and depends on services focused on psychosocial rehabilitation. Healthcare providers must encourage women to adopt strategies to promote their self-care. The psychological support group is a resource that helps women to face the long journey of treatment. This study aimed to understand the meanings women with breast cancer produced about their participation in a support group. This exploratory cross-sectional study was carried out with 10 women with breast cancer who use a rehabilitation service for mastectomized patients. Grounded Theory was used as a methodological reference. An open in-depth interview was applied for data collection. The contents were transcribed and coded. Inductive analysis and the constant comparison method were applied in the open, axial, and selective coding processes, which enabled the identification of three core categories: perception of the activities carried out in the group, identification of benefits and barriers of living in the group, and transformations resulting from participation. Participants denote their involvement with the group as a source of shelter, support, development of personal resources and friendships that helps promoting quality of life. Besides these potential benefits, participants also evinced barriers that can hinder adherence and continuity of participation in the group, suggesting the importance of incorporating a look at the subjective dimensions of women's health into care.(AU)

Sobrevivir al cáncer de mama es un problema de salud pública que depende de los servicios centrados en la rehabilitación psicosocial. Entre las necesidades identificadas en esta materia se encuentra el uso de estrategias para promover el autocuidado. Uno de los recursos que ayuda a afrontar el largo camino del tratamiento es el grupo de apoyo psicológico. El objetivo de este estudio es conocer los significados que producen las mujeres con cáncer de mama sobre su participación en un grupo de apoyo. Se trata de un estudio cualitativo, descriptivo y exploratorio, realizado con diez mujeres con cáncer de mama usuarias de un servicio de rehabilitación para mastectomizadas. Como referencia metodológica se utilizó la teoría fundamentada en los datos. Se aplicó una entrevista abierta en profundidad para la recogida de datos, cuyos contenidos fueron transcritos y codificados. El análisis inductivo y el método de comparación constante se aplicaron en los procesos de codificación abierta, axial y selectiva, lo que permitió identificar tres categorías centrales: percepción de las actividades realizadas en el grupo, identificación de los beneficios y las barreras de vivir en el grupo y transformaciones resultantes de la participación. Las mujeres denotan su participación en el grupo como una fuente de acogida, apoyo, desarrollo de recursos personales y amistades, que ayuda a promover la calidad de vida. Además de los beneficios potenciales, también se identificaron barreras que pueden dificultar la adherencia y continuidad de la participación en el grupo, lo que sugiere la necesidad de incorporar en la atención una mirada centrada en las dimensiones subjetivas de la salud de las mujeres.(AU)

Bombardier Blood (2020): Un documental más allá de la enfermedad / Bombardier Blood (2020): A Documentary beyond the Illness

Si bien la hemofilia era conocida como una enfermedad que perturbaba solo a las familias reales de Europa, actualmente afecta a uno de cada 5.000 y a uno de cada 30.000 varones recién nacidos vivos tanto para la de Tipo A como B, respectivamente. La hemofilia es un trastorno de la coagulación sanguínea que afecta principalmente a varones por su carácter de herencia recesiva ligada al X, siendo su manifestación principal las hemorragias que pueden llegar a ser mortales si no son tratadas correctamente. En Bombardier Blood (2020) de Patrick James Lynch, un documental enfocado al recorrido de Chris Bombardier, una persona hemofílica cuyo sueño es escalar las siete cumbres más altas del mundo, incluyendo en su paso el monte Everest en el Himalaya. El documental además de destacar los aspectos médicos sobre esta enfermedad hace ver los diferentes estilos de vida de acuerdo a su localización, las normativas y sistemas de salud que los rige y como esto incide en el diagnóstico, seguimiento y tratamiento. (AU)

While hemophilia was considered a disease that disturbed only the royal families of Europe, it currently affects one in 5.000 and one in 30.000 live newborn males for both Type A and B, respectively. Hemophilia is a blood clotting disorder that mainly affects men due to its character of recessive inheritance linked to X, its main manifestation hemorrhaging that can become fatal if they are not treated correctly. Bombardier Blood (2020) by Patrick James Lynch is a documentary focused on the journey of Chris Bombardier, a hemophilic person whose dream is to climb the seven highest summits in the world, including Mount Everest in the Himalayas. The documentary, in addition to highlighting the medical aspects of this disease, shows the different lifestyles according to their location, the regulations and health systems that govern them, and how these affect diagnosis, monitoring, and treatment. (AU)

"Not by a Decree of Fate:" Ellen Richards, Euthenics, and the Environment in the Progressive Era.

In 1904, Ellen Richards introduced "euthenics." By 1912, Lewellys Barker, director of medicine and physician-in-chief at Johns Hopkins Hospital, would tell the New York Times that the "task of eugenics" and the "task of euthenics" was the "Task for the Nation." Alongside the emergence of hereditarian eugenics, where fate was firmly rooted in heredity, this article places euthenics into the same Progressive Era demands for the scientific management over environmental issues like life and labor, health and hygiene, sewage and sanitation. I argue that euthenics not only heralded women as leaders in the quest for what Richards and eugenicists termed "racial improvement," but also aimed to make reforms through environmental and educational changes rather than hereditary interventions. Seeking to recuperate the figure of Ellen Richards in the history of science, I place Richards and her euthenics more into the debate over eugenics rather than over the emergence of home economics. Building on the work of Donald Opitz, Staffan Bergwik, and Brigette Van Tiggelen, this article shows, first, how Richards' career threads the needle between the home and the laboratory as sites of science making, not as separate spheres but as overlapping realms, and helps recover how domestic concerns shaped the focus of the life sciences. Second, this article shows how euthenics shaped eugenics by looking at the writings of American eugenicists Charles Davenport, Paul Popenoe, and David Starr Jordan. Third, the article describes how euthenics took root in new academic departments of domestic science, home economics, and departments child welfare and family life in the 1920 and 1930s, most notably the department of euthenics at the Kansas State Agricultural College from 1926 and the Institute of Euthenics at Vassar College after 1923.

Heredity of Schizophrenia in India: A 1928 debate.

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.

Heredity of pregnancy-related pelvic girdle pain in Sweden.

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.

PKD1 Nonsense Variant in a Lagotto Romagnolo Family with Polycystic Kidney Disease.

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.