Genealogical Data Research Articles

Examining the trade-offs between human fertility and longevity over three centuries using crowdsourced genealogy data.

The evolution theory of ageing predicts that reproduction comes with long-term costs of survival. However, empirical studies in human species report mixed findings of the relationship between fertility and longevity, which varies by populations, time periods, and individual characteristics. One explanation underscores that changes in survival conditions over historical periods can moderate the negative effect of human fertility on longevity. This study investigates the fertility-longevity relationship in Europe during a period of rapid modernisation (seventeenth to twentieth centuries) and emphasises the dynamics across generations. Using a crowdsourced genealogy dataset from the FamiLinx project, our sample consists of 81,924 women and 103,642 men born between 1601 and 1910 across 16 European countries. Results from multilevel analyses show that higher fertility has a significantly negative effect on longevity. For both women and men, the negative effects are stronger among the older cohorts and have reduced over time. Moreover, we find similar trends in the dynamic associations between fertility and longevity across four geographical regions in Europe. Findings and limitations of this study call for further investigations into the historical dynamics of multiple mechanisms behind the human evolution of ageing.

Kinship and the familial occurrence of skeletal developmental anomalies in the noble Swéerts-Sporck family (Bohemia, 17th to 20th centuries)

ObjectiveTo determine the degree of similarity of biologically related individuals according to the occurrence of skeletal developmental anomalies (SDA), to see whether these anomalies reflect documented biological relationships. Material and methodsThe sample consists of the skeletal remains of seven members of the noble Swéerts-Sporck family from the 17th-20th centuries. Eighty-nine SDA were examined using morphological assessment, X-ray and CT. The degree of similarity was calculated using a similarity coefficient (Cvrček et al., 2018). ResultsThere were three shared SDA in the sample (cranial shift at the C-T border, cervical ribs, hypoplasia of rib 12), and another fifteen individual SDA were reported. The degree of similarity between individuals supports their documented relationships. The greatest similarity was found in closely related individuals such as father/son or siblings, and the least between unrelated individuals. ConclusionsSDA can be used as a supportive tool for detecting family relationships. The results correspond to the conclusions of earlier analyses of non-metric traits and frontal sinuses in the same sample: the smaller the biological distance between individuals, the greater the degree of their similarity. SignificanceUsing unique human skeletal collections, this communication contributes to the expansion of knowledge about the familial occurrence of SDA. LimitationsThe small number of individuals limits the use of statistical approaches. Suggestions for further researchThe results call for research on this topic using a larger sample with known genealogical data and the same approaches, to confirm our conclusions.

Familial occurrence of skeletal developmental anomalies as a reflection of biological relationships in a genealogically documented Central European sample (19th to 20th centuries).

Skeletal developmental anomalies (SDA) are a subject of constant interest across scientific disciplines, but still mostly as isolates and curiosities. The aim of this study was to find out to what extent the occurrence of SDA reflects documented biological relationships. The skeletal remains of 34 individuals with known genealogical data were available, members of one family over four generations (19th to 20th centuries, Bohemia, Czech Republic), including some inbred individuals. The occurrence of 89 SDA was assessed on the basis of scopic morphological evaluation and X-ray and CT examinations. The degree of similarity between individuals was calculated using a "similarity coefficient" (SC). A linear model was used to test the relationship between positive values of the SC and the relatedness of biologically related individuals. Simultaneously, based on population frequencies of the evaluated anomalies, those that could be considered familial were recorded. A statistically significant relationship between morphological similarity and the biological distance between individuals was found. The greatest similarity was found among close relatives such as parents and children, siblings, or grandparents and grandchildren. The effect of increased consanguinity on the occurrence of anomalies was not confirmed, however. Seventeen SDA shared by closely related individuals were found in the sample, supporting the documented family relationships among them. Eleven of these were selected as possibly familial, but only five were statistically significant: an elongated styloid process, a cervical block vertebrae (arch, facet joints), hamate hamulus aplasia, anteater nose sign, and incomplete fusion of the S1spinous process. There were also 28 cases of individual occurrences of 17 different SDA, without connection to the documented relationships between individuals.

Challenging the Fundamental Premise of White Supremacy: DNA Documents the Jewish Origins of the New England Colony

The English Puritans of New England are a foundational element in the current racist ideology of White Supremacy. Depicted in history books as stalwart British Protestants who braved bitter winters and Native predations to establish a “City on the Hill”—a beacon to the world of freedom and liberty—the Puritans became ideals in the American consciousness. But what if this is a misrepresentation, created largely in the mid and late 1800s to serve as a political barrier against Catholic, East European, Jewish, and Asian immigrants who threatened the “American way of life”? The present research uses genealogical DNA data collected from descendants of the New England settlers to demonstrate that these original “Yankees” were of Jewish ancestry. The WASP origination of New England is shown to be a false narrative.

A genealogical survey on the main bloodline of the Australian Cattle Dog in Italy

This paper presents the results of genetic variability analyses using genealogical data on the main genetic bloodline of the Australian Cattle Dog in Italy, a line that has had a significant impact on the development of the breed. All the genealogical data on the progeny and ancestors of one of the first stallions introduced in Italy were considered, i.e. Cattlefarm's Comeback Jack born on 1/2/1997 in Finland. Animals from the bloodline born between 1962 and 2019 were considered. A total number of 1722 animals were found to be from the line which represents the entire population (WP), including the basic population (BP) and the reference population (RP) defined as the animals currently living. A total of 982 animals were in the RP, with the oldest living dogs born in 2004. A total of 854 dogs were inbred. The average inbreeding coefficient (F) in the RP was 5.1%, while the average inbreeding of the inbred animals was 5.8%. The F was < 0.10 in 711 dogs (77.3% of inbred), and > 0.20 in only 36 dogs (3.91% of inbred). Fifteen traced generations were highlighted. A maximum average inbreeding value (6.45%) was observed in the dogs with 11 traced generations. This research highlighted the good genetic variability of this Australian Cattle Dog bloodline thanks to the efficient management of the breeders who in the past introduced some stallions from abroad. Currently, the lines in Italy are not sufficiently high to prevent inbreeding in the new matings, which is becoming frequent. It is, therefore, important to continue to import new stallions for reproduction to expand the genetic variability. However, at the same time, the old lines need to be preserved genetically, aptitudinally and morphologically, as they are an important heritage of the breed in Italy.

Assessment of Facial Homogeneity with Regard to Genealogical Aspects Based on Deep Learning Approach

The current research work encompasses the assessment of similarity based facial features of images with erected method so as to determines the genealogical similarity. It is based on the principle of grouping the closer features, as compared to those which are away from the predefined threshold for a better ascertainment of the extracted features. The system developed is trained using deep learning-oriented architecture incorporating these closer features for a binary classification of the subjects considered into genealogic non-genealogic. The genealogic set of data is further used to calculate the percentage of similarity with erected methods. The present work considered XX datasets from XXXX source for the assessment of facial similarities. The results portrayed an accuracy of 96.3% for genealogic data, the salient among them being those of father-daughter (98.1%), father-son(98.3%), mother-daughter(96.6%), mother-son(96.1%) genealogy in case of the datasets from “kinface W-I”. Extending this work onto “kinface W-II” set of data, the results were promising with father-daughter(98.5%), father-son(96.7%), mother-daughter(93.4%) and mother-son(98.9%) genealogy. Such an approach could be further extended to larger database so as to assess the genealogical similarity with the aid of machine-learning algorithms.

Database of Buryat Genealogies: Major Approaches and Implementation

The article develops a database of archival sources covering Buryat family trees. Genealogic data were traditionally very important for Buryat society as they were linked to such aspects as administrative arrangement, economic activity and marital relations. Special importance of family relations in social organization was seen in spiritual life as it actualized the cult of ancestors. In the context of ethnocultural revival observed in the recent decades, the social significance of information resources on Buryat genealogies is increasing. The funds of the Center for Oriental Manuscripts and Xylographs of the IMBT SB RAS store a large number of materials on this topic. They were the basis the discussed database was developed on. To form a meta-collection of archival materials on this topic the authors used corpus analysis methods processing the general index formed on the basis of electronic archival cases titles of the Center for Oriental Manuscripts and Xylographs. To organize the data the methodology of authority control is applied. The ontology scheme of a family tree includes descriptive categories "Family", "Place", "Person". This makes it possible to implement user-friendly methods of data aggregation and visualization - GIS, hierarchical trees, social graphs, etc. which are integrated into a web application. Digitalization of archival and rare book funds contributes to the identification and formation of thematic meta-collections similar to the corpus of archival sources on Buryat genealogies considered in this article. This opens up new opportunities for a comprehensive disclosure of historical and cultural heritage.

Features of the influence of hereditary factors on the clinical manifestations of depressive disorders

IntroductionThe urgency of the problem of depression is due to their high prevalence and severity of consequences. At present, the pathogenetic role of heredity in the course of depressive disorders remains unclear. Therefore, studies related to this problem are designed to identify the relationship between hereditary factors and the characteristics of the clinic of depression.ObjectivesThe aim was to study the features of the influence of hereditary factors on the clinic of depressive disorders.Methodsclinical-psychopathological, psychometric, genealogical, statistical.ResultsBased on the study of clinical, psychometric (Hamilton scale (HDRS)), genealogical data of 87 patients with depression, a high level of family burden of depression at all levels of kinship in the pedigree of patients (73.56%), alcohol abuse (39.08%), the presence of hypertension (54.02%), heart disease (42.53%) and endocrine pathology (14.94%) were identified. Moreover, in the pedigree of the examined most often this pathology was found in relatives of I and II degree of kinship. When comparing the factors of heredity with the clinical structure and features of depression revealed the proportion of correlations of such factors as: observation by a psychiatrist of I and II degree of relatedness (p ≤ 0.01), depressive disorders mainly by II degree of relatedness (p ≤ 0.05), suicidal behavior according to I and II degree of kinship (p ≤ 0.005), alcohol dependence mainly on I degree of kinship (p ≤ 0.03). Selected leading symptom complexes: depressive, asthenic, apathetic, anxiety-phobic, somato-vegetative, hypochondriac.ConclusionsThe data obtained should be taken into account in diagnostic and preventive measures.

Research of Collection Arrangement of Gelao 's Genealogy

The Gelao nationality is one of the oldest minorities in southern China recognized by the academic circles. However, up to now, the genealogical research of Gelao nationality is still very weak. The reason is that the genealogical data of the Gelao nationality is extremely scarce at present, which seriously affects the development of relevant research. Therefore, it is urgent to collect and sort out the genealogy of the Gelao nationality in a comprehensive and systematic manner. The genealogy research of Gelao nationality will use the following methods: the combination of document acquisition method and field survey method; digital collection method; document cataloging method and summary method; content analysis and value analysis; intra-ethnic and inter-ethnic comparative analysis. The Gelao genealogy research has several academic values: it provides solid data support for related research in philology, ethnology, history, and other disciplines; it helps to expand the research scope and field of genealogy; it helps to promote the in-depth development of Gelao studies. The practical significance of the study of Gelao genealogy: it helps to promote family construction in Gelao areas; it helps to enhance the cultural confidence of Gelao people and maintain the harmony and stability of Gelao areas.

Lower total motile count is associated with smaller historic intergenerational family size: a pedigree analysis from the Utah Population Database.

To describe the association between contemporary total motile count (TMC), a measure of male factor infertility, and historic intergenerational family size. This is a retrospective, population-based, cohort study of men who underwent semen analysis for infertility workup at University of Utah, with at least a single measure of TMC, who were linked to extensive genealogical data. Two thousand one hundred eighty-two pedigree branches of men with a measure of TMC within the UPDB were identified. We identified the average number of generations and offspring within each generation. Conditional logistic regression models were used to assess the association between the risk of having a TMC in the 5th or 25th percentile and intergenerational family size. Generalized estimating equations (GEE) were used to assess the association between interval-level TMC and the number of ancestral offspring. We found no association between intergenerational size and TMC within the 5th percentile (TMC < 4 million; RR = 0.97, 95% CI 0.93-1.01) or the 25th percentile (TMC < 62 million; RR = 1.00, 95% CI 0.97-1.03). When TMC was analyzed as a continuous variable, we found that lower TMC is associated with smaller intergenerational family size. For every additional child in their ancestral pedigree, we observed an increase in TMC of 1.88 million (p = 0.03). Men in the top quartile for intergenerational family size had a TMC that was 48 million higher than men in the bottom quartile (p = 0.047). We found an association between TMC and ancestral family size, suggesting that lower TMC is associated with smaller intergenerational family size.

Development of the Genealogical FamilySearch Database and Expanding Its Use to Map and Measure Multiple Generations of American Migration

Genealogical research is full of opportunities for connecting generations. Millions of people pursue that purpose as they put together family trees that span hundreds of years. These data are valuable in linking people to the people of their past and in developing personal identities, and they can also be used in other ways. The purposes of this paper are to first give a short history of the development and practice of family history and genealogical research in the Church of Jesus Christ of Latter-day Saints, which has developed the FamilySearch website, and second, to show how genealogical data can illustrate forward generation migration flows across the United States by analyzing resulting patterns and statistics. For example, descendants of people born in several large cities exhibited distinct geographies of migration away from the cities of their forebears.

Knowledge Graph for China's Genealogy

Genealogical knowledge graphs depict the relationships of family networks and the development of family histories. They can help researchers to analyze and understand genealogical data, search for genealogical descendant paths, and explore the origins of a family more easily. However, the heterogenous, autonomous, complex, and evolving natures of genealogical data bring challenges to the development of contemporary genealogical knowledge graph models. Applying existing methods to genealogical data may be improper because general knowledge graph models lack in-depth domain knowledge. In this paper, we propose a genealogical knowledge graph model named Huapu-KG that combines HAO intelligence (human intelligence + artificial intelligence + organizational intelligence) to implement the construction and applications of genealogical knowledge graphs. Furthermore, challenges in constructing genealogical knowledge graphs are demonstrated, and experiments conducted on real-world genealogical datasets verify the feasibility and effectiveness of our proposed model.

Childless Aristocrats: Inheritance and the Extensive Margin of Fertility

Abstract Using genealogical data of British aristocrats, we show that inheritances can affect childlessness. We study settlements, a contract restricting heirs’ powers and settling bequests for yet-to-be-born generations. Settlements reduced childlessness to the ‘natural’ rate, ensuring aristocratic dynasties’ survival. Our estimation exploits that settlements were signed at the heir’s wedding if the family head lived until this date. Whether the heir was born after a girl provides as-good-as-random assignment into settlements. Next, we develop a theory that reproduces our findings, shows that exponential discounting cannot rationalise inheritance systems restricting heirs and that inheritance systems can emerge endogenously when fertility concerns exist.

A atividade artística do ensamblador Francisco Gonçalves Pombo na diocese de Coimbra

Nos últimos anos, temos trazido ao conhecimento da comunidade científica e público em geral, vários estudos sobre artistas pouco conhecidos ou mesmos desconhecidos, através de investigações respeitantes à História da Arte em Portugal. Muitos destes artistas fizeram o seu percurso de vida e artístico na região centro do nosso país, em particular na diocese de Coimbra.&#x0D; Neste contexto, salientamos o escultor vimaranense Francisco Gonçalves Pombo que, fixando-se na cidade de Coimbra, executou diversas empreitadas artísticas na região centro de Portugal.&#x0D; Com este estudo, iremos apresentar um conjunto de dados genealógicos relativos a este escultor, assim como alguns contratos de importância manifesta relativos à sua atividade.

Frontal sinus anatomy of the noble Swéerts-Sporck family and verification of their biological relationships using similarity analysis.

The evaluation of frontal sinus similarity is one way to detect biological relationships, especially in small groups, including families of historically known personalities. However, possibilities for studying this issue are currently limited. This contribution deals with the frontal sinuses of a rare osteological sample with known genealogical data, members of the noble Swéerts-Sporck family from the 17th to 20th centuries. The aim is to verify whether the frontal sinuses reflect documented family relationships. Basic dimensions of the frontal sinus such as total surface area and volume, and maximum height and width, and also morphology and anatomical features were evaluated using computed tomography scans. The portions of the frontal sinus above the "external supraorbital line" were analyzed. The degree of similarity between biologically related individuals was determined for each variable and compared with their known biological distance. The degree of similarity based on dimensions was evaluated using both the unadjusted measured data and standardized data adjusted to size. For the unadjusted dimensions, a positive correlation between morphological similarity and biological relatedness was apparent. On the other hand, no positive correlation was apparent for most of the standardized data. Only total volume showed a very weak indication of a positive trend in the standardized data, but this was weaker than in the original values. A positive quantifiable relationship between morphological patterns and biological distance is not clearly indicated. However, nonmetric features do support the documented relationships of the individuals.

Precise natal homing and an estimate of age at sexual maturity in hawksbill turtles

AbstractThe geographic specificity of natal philopatry (how precisely breeding individuals return to their natal origins) influences breeding biology, genetic diversity and habitat range, and therefore has important implications for species resiliency and management. Also, the age at which individuals reach sexual maturity and enter the breeding population is a vital parameter for demographic analyses. Empirical research on philopatry and maturation, however, is challenging for long‐lived animals that are difficult to observe, such as marine turtles that have complex oceanic life histories. Regional natal philopatry is well established for marine turtles, but the geographic specificity of philopatry is unclear. Similarly, estimates of age at maturity vary widely, and direct evidence is lacking. Here, we targeted these information gaps by assessing kinship among 256 females from Antigua’s Jumby Bay (JB) hawksbill turtle rookery, a population with demonstrated nest‐site fidelity and neophyte assimilation. We estimated mother–daughter and full sibling relationships with a maximum‐likelihood full‐pedigree reconstruction approach, incorporating genotypic (12 microsatellites), maternal genealogy (mitochondrial DNA) and age structure (long‐term mark–recapture) data. We validated relationships with parentage assignment and pairwise relatedness estimators. Fourteen veteran nesters were the mothers of 42 younger nesters, and 94 nesters formed 35 full sibships. Time between the first nesting records of mothers and their daughters indicated maximum time to maturity as short as 14 years in Caribbean hawksbills. Thirteen of the 14 mothers showed consistently high fidelity to JB for two decades, providing compelling evidence that 41 of these daughters originated from JB nests and returned to this 1‐km‐long natal site to breed. Rookeries with strongly philopatric individuals might have limited colonization potential and be at a disadvantage in the event of habitat loss. This study demonstrates the utility of long‐term mark–recapture data in kinship analyses for answering questions relevant to endangered species conservation.

Genomic Characterization of the Istrian Shorthaired Hound.

Simple SummaryIstrian shorthaired hound is an old indigenous Croatian dog breed. However, there is no data available about its genetic diversity, population structure, and inbreeding level, which would be needed for advanced management and conservation of this breed. We studied the population structure using 220K SNP array and compared the genomic data with the genealogical records. This allowed us to place Istrian shorthaired hound on the map of the world dog populations. The Istrian shorthaired hound has a relatively high effective population size and low level of inbreeding. Its genome contains a higher number of short runs of homozygosity compared to other analysed breeds, thus confirming the old origin of the breed and balanced use of breeding animals. The breed was placed in the same clade with Italian hunting breeds suggesting that the Istrian shorthaired hound was probably used for the development of some of these breeds. The genomic analysis importantly contributes to the development of future breeding strategies and supports the conservation of the Istrian shorthaired hound.Istrian shorthaired hound is an old indigenous Croatian dog breed with historical traces of its origin, which date back to the 14th century. Due to its intelligence and great hunting abilities, it is considered an excellent hunting dog. Despite its ancient origin, there is no data on genetic diversity, population structure, and degree of inbreeding that could be used for advanced management and conservation of this breed. Our study aimed to provide a high-resolution population structure of the Istrian shorthaired hound using a 220K HD SNP array, to compare the obtained data with the genealogical records and to place the breed in a broader context of world dog populations. Relatively high population size and low inbreeding coefficient estimated from genealogical data indicate a preserved genetic diversity in this breed. The principle component analysis, the NeighborNet network, and TreeMix were used to determine the genetic relationship between the Istrian shorthaired hound and other breeds. The Istrian shorthaired hound was found to be genetically related to Italian hunting dogs sharing the same branch with the Segugio Italiano a Pelo Raso and Segugio Italiano a Pelo Forte. The ADMIXTURE analysis indicated that the Istrian shorthaired hound could be involved in the development of some other hunting dog breeds. The estimated effective population size (Ne) based on SNP data was similar to Ne calculated from genealogical data indicating the absence of bottlenecks and well-balanced use of breeding animals. The low genomic inbreeding coefficient, together with the higher number of short runs of homozygosity, observed in the Istrian shorthaired hound, confirms the ancient origin of the breed based on historical documents. The analysis of selective sweeps identified genomic regions with the strongest selection signals in the vicinity of the genes associated with cognitive performance and behavior. Genome analysis proved to be a useful tool for estimating population parameters and can be implemented in the conservation plan for this indigenous breed.

Genetic diversity and validation of a microsatellite panel for parentage testing for alpacas (Vicugna pacos) on three Peruvian farms

• There is a high genetic diversity within and among the three alpaca farms. • The inbreeding levels of the three alpaca farms are moderate. • A panel of 15 microsatellite markers have been validated for parentage control in Peruvian alpaca farms. The alpaca is of greatest economic importance in the Peruvian High Andes. This study aimed to determine the genetic diversity of three Peruvian alpaca farms, as well as, to validate a microsatellite markers panel for paternity testing. In this study, 247 samples of Huacaya alpacas were taken from three different localities (Sanjo, San Pedro de Raco and Cachipampa) from Pasco Region in Peru. DNA was obtained from hair follicles and genotyped for 15 microsatellites markers in multiplex electrophoresis runs. A total of 225 alleles were detected across the 15 loci investigated. The polymorphism information content considering all loci was 0.82, which indicated that the microsatellite panel was very polymorphic and highly informative. The estimated diversity parameter showed that farms have high levels of genetic diversity (H E = 0.826), and revealed the existence of genetic differentiation among the farms ( F ST = 2.8 %). The highest inbreeding coefficient was in the Sanjo farm ( F IS = 0.303). The results of the parentage testing indicated that all loci showed values greater than 70 % probability of discrimination. However, the highest values found were 94 % (YWLL08) and 90 % (YWLL36). The average of the probability of exclusion obtained was 0.999994 if the genotype for one alleged parents is known, and 0.99999 if the genotypes for both alleged parents are known. The results obtained show that there is a high genetic diversity and validate the panel of microsatellite markers, that would help to improve the identification system and genealogical data collection.

Vēsturiskie ciemu nosaukumi Piejūras reģionālajā parkā: kuršu un kursenieku pēdas Klaipēdas apkārtnē

The paper deals with the analysis of the toponyms of the historical Klaipėda region (Ger. Memelland), the northern part of former East Prussia. Research material comes from historical and cartographic sources of various periods. The accessibility of these sources enables marked expansion of the data that was used by the initiators of this theme in the middle of the twentieth century. A fairly small seaside territory (2,735 ha in the mainland), in which the concept of the regional park is directly related to the protection of cultural heritage, was selected for research. Methods of diachronic and comparative linguistics, as well as of geolinguistics, are combined with analysis of historical and genealogical data. Special attention is paid to the traces of fifteenth-to-eighteenth-century migration from Courland in the onomastics in the Klaipėda region. The problem of regional lexical identification, investigation of the chronology of the documentation of names, and the search for specific linguistic features addressed in the paper allow raising the hypotheses of the origin and the interaction of languages. The actualisation of historical and obsolete names for the needs of the Baltic, historical, and cultural studies is approached as an important issue. In the sixteenth century, the northern part of Prussia was a zone of intensive contacts of the Baltic languages. The personal names recorded here at that time point to undisputed links between the dialects of Courland and north-western Lithuanians. Now it is difficult to say which part of the toponyms has reached us from the old Curonians and which toponyms immigrated from Courland – not only due to the hypothetical nature of the reconstructed system of close languages, but also because analysis is made complicated by varying orthography in German characters. In the seventeenth century and later, the expansion of Latvian onomastics in the Klaipėda region decreased, but even then, there would appear names the etymology of which is more transparent in Latvian and not Lithuanian. The influence of Curonian and neo-Curonian (the Kursenieku language) is stronger in the seaside territories of fishermen and in the locations where fishermen became assimilated in the farmers’ community. However, the names of the villages situated at some distance from the sea are more frequently related to Lithuanian anthroponyms. In the northern part of the Klaipėda region, German toponyms were rare exceptions even during the period of intensive germanization. Although in the early twentieth century, the origin of the official oikonyms used in the Lithuanian and German environment often differed, the absolute majority of German oikonyms are of Baltic origin. Lituanization of the names of villages was a natural result of the residents’ assimilation process. In the process of the reconstruction of historical toponyms, it is possible to form a reserve list of names, part of which could be brought back for ‘the second life’ by giving these names to streets, parts of the regional park, hotels, and other objects.

Segregation analysis of the BRCA2 c.9227G>T variant in multiple families suggests a pathogenic role in breast and ovarian cancer predisposition

Classification of variants in the BRCA1 and BRCA2 genes has a major impact on the clinical management of subjects at high risk for breast and ovarian cancer. The identification of a pathogenic variant allows for early detection/prevention strategies in healthy carriers as well as targeted treatments in patients affected by BRCA-associated tumors. The BRCA2 c.9227G>T p.(Gly3076Val) variant recurs in families from Northeast Italy and is rarely reported in international databases. This variant substitutes the evolutionary invariant glycine 3076 with a valine in the DNA binding domain of the BRCA2 protein, thus suggesting a high probability of pathogenicity. We analysed clinical and genealogic data of carriers from 15 breast/ovarian cancer families in whom no other pathogenic variants were detected. The variant was shown to co-segregate with breast and ovarian cancer in the most informative families. Combined segregation data led to a likelihood ratio of 81,527:1 of pathogenicity vs. neutrality. We conclude that c.9227G>T is a BRCA2 pathogenic variant that recurs in Northeast Italy. It can now be safely used for the predictive testing of healthy family members to guide preventive surgery and/or early tumor detection strategies, as well as for PARP inhibitors treatments in patients with BRCA2-associated tumors.