Pedigree Analysis Research Articles

Inferring Distant Relationships From Dense SNP Data Utilizing Two Genealogy Algorithms.

A highly esteemed method known as investigative genetic genealogy (IGG) has been developed to identify DNA samples from forensic crime scenes and human remains of disaster victims. With the advent of next-generation sequencing, it is now feasible to access information on millions of SNPs typed in a single sequencing run that fulfill the requirements for kinship inference. However, challenges such as the poor quality of forensic samples, the high cost associated with sequencing technology, and privacy concerns regarding large-scale genetic databases remain unresolved in this field. In the present study, we validated the identification of relationships up to the seventh degree using two genealogy algorithms (IBIS and KING) under various parameter settings. This was accomplished through whole genome sequencing data derived from two southern Chinese Han pedigrees during an initial phase, while also exploring workflows adapted for low-quality samples. To achieve this objective, low-coverage whole genome sequencing data were downsampled from high-coverage original datasets; additionally, mimic SNP array data-containing less information but offering greater accessibility-were prepared as reference samples. Through a series of experimental analyses, we not only validate the applicability of selected processing procedures and inference tools for low-coverage samples but also proposed that a meticulously crafted site filtering strategy can significantly improve the accuracy of kinship identification. This acknowledges the necessity for further systematic evidence in future research endeavors.

Mexican Health and Aging Study Biomarker and Genetic Data Profile.

The Mexican Health and Aging Study (MHAS) is one of the largest ongoing longitudinal studies of aging in Latin America, with six waves over 20 years. MHAS includes sociodemographic, economic, and health data from a nationally representative sample of adults 50 years and older in urban and rural Mexico. MHAS is designed to study the impact of diseases on adults' health, function, and mortality. As Mexico is experiencing rapid population aging, providing adequate information to study this phenomenon is vital for designing and implementing public policies. The availability of biomarker and genetic data and longitudinal survey data elevates opportunities for research on aging in a low-middle-income country. This manuscript describes the profile of biomarkers and genetic data available in the MHAS study, including sample sizes and sociodemographic characteristics of participants who provided biospecimens for biomarker analyses, emphasizing recent genetic data. The sample size of individuals with anthropometric biomarkers was 2 707 (Wave 1-2001), 2 361 (Wave 2-2003), 2 086 (Wave 3-2012), and 2 051 (2016). Capillary blood samples were collected from 2 063 participants in 2012 (Wave 3) and 1 141 in 2016. Venous blood samples for blood-based biomarkers were collected from 2 003 participants in 2012 (Wave 3) and 752 in 2016. Venous blood samples were also collected for genetic data from 2 010 participants in 2012 (Wave 3) and 750 in 2016. A total of 7 821 participants provided saliva in 2018, and 2 671 provided hair in 2018. From these samples, a total of 7 204 have genome-wide genetic data, 8 600 have apolipoprotein-E genotype data, and 7 156 have genetic ancestry data.

Analysis of a Chinese pedigree with female infertility due to WEE2 gene c.495del homozygous frameshifting variant induced fertilization disorder

To explore the genetic basis for a patient with repeated fertilization failure during assisted reproductive therapy, and to identify the source and mode of mutation. A couple treated at the Center for Reproductive Medicine, Gansu Provincial Maternal and Child Health Care Hospital in January 2024 for infertility with incomplete left tube obstruction was selected as the study subject. Relevant clinical data was collected. The couple was subjected to whole exome sequencing (WES), and the candidate variant was verified by Sanger sequencing of their family members and bioinformatic analysis. WES has identified a homozygous c.495del frameshifting mutation of the WEE2 gene in the female partner, whilst no relevant variant was suspected in the male partner. The elder brother of the female partner was homozygous for the above variant, while her parents, maternal and paternal aunts, uncle, grandmother, and grandmother were heterozygous for it. Based on the guidelines from the American College of Medical Genetics and Genomics, above variant was rated to be pathogenic. The homozygous c.495del frameshifting mutation of the WEE2 gene probably underlay the oocyte fertilization disorder in this couple, which has conformed to an autosomal recessive inheritance.

Inference of genetic ancestry from a multi-gene cancer panel in Colombian women with cancer.

Cancer health disparities among racial and ethnic populations significantly burden health systems due to unequal access to early detection, treatment, and healthcare resources. These disparities lead to worse outcomes and increased costs from delayed diagnoses, advanced treatments, and prolonged care. Genetic differences can also influence cancer susceptibility and treatment response, thus analyzing genetic ancestry is essential for uncovering genetic factors that may contribute to these disparities. Utilizing data from clinical multigene cancer panels to infer genetic ancestry offers a valuable approach to understand population structure and the impact of individual ancestries in development of complex diseases. To evaluate the accuracy of global ancestry inference using genetic markers from the TruSight™ Hereditary Cancer Panel, which was used to investigate hereditary cancer syndromes in a cohort of 116 female cancer patients at the Colombian National Cancer Institute. Additionally, to compare these results with genetic ancestry estimations from traditional genome-wide markers. Our results demonstrate a strong correlation between global genetic ancestry inferred with markers captured from TruSightTM panel (4785 markers) and Whole Genome Sequencing (WGS, 8 million markers in admixed populations. The correlation values were 0.96 (p < 0.0001) for the Native American and European ancestry components, and 0.99 (p < 0.0001) for the African ancestry fraction. Genetic ancestry mean proportions in the Colombian cohort were 45.7%, 46.2%, and 8.11% for the European, the Native American, and the African components, respectively. This study demonstrates the accuracy of ancestry inference from clinical panel data offering a promising approach for understanding cancer health disparities in admixed populations.

Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P)or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives. We used the phenomenon of purifying hyperselection, which acts to decrease the frequency of SCGD causal diplotypes, to reduce false positives. Training of gene-disease-inheritance mode-diplotype tetrads in 618,290 control and affected subjects identified 293 variants or haplotypes and seven genes with variable inheritance contributing higher positive diplotype counts than consistent with purifying hyperselection and with little or no evidence of SCGD causality. With these changes, 2.0% of UKB470K adults were positive. In contrast, gNBS was positive in 7.2% of 3,118 critically ill children with suspected SCGDs and 7.9% of 705 infant deaths. When compared with rapid diagnostic genome sequencing (RDGS), gNBS had 99.1% recall. In eight true-positive children, gNBS was projected to decrease time to diagnosis by a median of 121days and avoid life-threatening disease presentations in four children, organ damage in six children, ∼$1.25 million in healthcare cost, and ten (1.4%) infant deaths. Federated training predicated on purifying hyperselection provides a general framework to attain high precision in population screening. Federated training across many biobanks and clinical trials can provide a privacy-preserving mechanism for qualification of gNBS in diverse genetic ancestries.

When Two Worlds Collide: The Potential Lifesaving Convergence of Genetic Genealogy and Molecular Diagnostics-An Interview with Brian H. Shirts, MD, PhD

When Two Worlds Collide: The Potential Lifesaving Convergence of Genetic Genealogy and Molecular Diagnostics-An Interview with Brian H. Shirts, MD, PhD

Genetic Analysis and Reproductive Interventions for Two Rare Families Affected by Severe Haemophilia A.

Haemophilia A (HA) is a rare bleeding disorder caused by variants in F8. Although traditional mutational analyses have identified numerous pathogenic variants, the aetiology of HA in certain patients remains unclear. Furthermore, female patients with severe HA are rare. To investigate the molecular defects underlying severe HA in two patients and provide personalised reproductive interventions for their families. Two patients diagnosed with severe HA without other clinical phenotypes were enrolled in the study. A combination of whole-exome sequencing, real-time quantitative polymerase chain reaction and long-read sequencing (LR-sequencing) was performed to reveal the molecular defects of them, followed by the application of different reproductive intervention strategies. Proband 1, a 29-year-old man with FVIII activity of 0.8%, did not exhibit common F8 variants, including Inv1 or Inv22, in the coding region. However, he carried a rare maternal novel inversion on ChrX:154148973_154170321, spanning approximately 21.345Kbp, with breakpoints in introns 13 and 14 of F8. Finally, the couple of Proband 1 opted for assisted reproductive technology using preimplantation genetic testing and successfully conceived. Proband 2, a 20-year-old female with severe HA and FVIII activity of 0.6%, carried inv22 of F8. Further investigation combining whole exome sequencing (WES) and pedigree analysis revealed that she carried a maternal cross-deletion encompassing exons 1-22 of F8, FUNDC2, BRCC3 and CLIC2, along with a de novo missense variant c.5852T>C (p.Leu1951Ser) on her paternal X-chromosome. Chromosome X-inactivation (XCI) analysis demonstrated a highly skewed inactivation of the maternal X chromosome, with a ratio of 98:2. Subsequently, prenatal diagnosis confirmed that the third child in this family did not carry any of the F8 variants present in Proband 2. Our findings provide novel insights into the genetic aetiology of HA and emphasise the importance of a definitive diagnosis in guiding genetic counselling and personalised reproductive interventions for affected individuals and their families.

Using multiplexed functional data to reduce variant classification inequities in underrepresented populations

BackgroundMultiplexed Assays of Variant Effects (MAVEs) can test all possible single variants in a gene of interest. The resulting saturation-style functional data may help resolve variant classification disparities between populations, especially for Variants of Uncertain Significance (VUS).MethodsWe analyzed clinical significance classifications in 213,663 individuals of European-like genetic ancestry versus 206,975 individuals of non-European-like genetic ancestry from All of Us and the Genome Aggregation Database. Then, we incorporated clinically calibrated MAVE data into the Clinical Genome Resource’s Variant Curation Expert Panel rules to automate VUS reclassification for BRCA1, TP53, and PTEN.ResultsUsing two orthogonal statistical approaches, we show a higher prevalence (p ≤ 5.95e − 06) of VUS in individuals of non-European-like genetic ancestry across all medical specialties assessed in all three databases. Further, in the non-European-like genetic ancestry group, higher rates of Benign or Likely Benign and variants with no clinical designation (p ≤ 2.5e − 05) were found across many medical specialties, whereas Pathogenic or Likely Pathogenic assignments were increased in individuals of European-like genetic ancestry (p ≤ 2.5e − 05). Using MAVE data, we reclassified VUS in individuals of non-European-like genetic ancestry at a significantly higher rate in comparison to reclassified VUS from European-like genetic ancestry (p = 9.1e − 03) effectively compensating for the VUS disparity. Further, essential code analysis showed equitable impact of MAVE evidence codes but inequitable impact of allele frequency (p = 7.47e − 06) and computational predictor (p = 6.92e − 05) evidence codes for individuals of non-European-like genetic ancestry.ConclusionsGeneration of saturation-style MAVE data should be a priority to reduce VUS disparities and produce equitable training data for future computational predictors.

Genetic pedigree analyses of Arctic grayling offspring produced to initiate the Michigan reintroduction program

Genetic pedigree analyses of Arctic grayling offspring produced to initiate the Michigan reintroduction program

Unveiling the Mysteries of Fractured Basement Oil Residues in the Upper Benue Trough, Nigeria

This study offers additional evidence for the occurrence of oil residues within fractures of the basement rocks in the Upper Benue Trough, Nigeria. The data suggests that the observed oil residues were originally generated as light oils, which were later biodegraded into heavy oils. These Upper Benue Trough's oil stains are a valuable tool for hydrocarbon exploration in the region as they indicate the existence of a petroleum system in the basin. We find a strong similarity to the proportions of C27, C28, and C29 regular steranes of oils found in the sandstones and shales of the Bima Formation in the Upper Benue Trough when we plot the relative quantities of these steranes of the investigated basement rock oil types on a ternary graph. This shows a positive correlation between the oils from the Bima Formation and the fractures found in the Precambrian basement rocks. Additionally, the studied basement oils and the oils extracted from the Bima Formation had comparable sterane maturity criteria. Again, trisnorhopane thermal indicators are also identical in the studied oils. The C3222S/(22R+22S) homohopane isomerization ratio and Ts: Tm ratio of the examined basement rock oils are similar to those of the oils extracted from the Bima Formation's shales, suggesting that the Bima Formation's shale is the primary source rock for the examined basement rock oils. Oils have also been reported to develop similarly in the Precambrian basement rocks of the Bongar Basin in the Chad Republic, known as basement-buried hills. As members of the West African rift basins, the Nigerian Upper Benue Trough and the Bongar Basin share genetic ancestry. As a result, we should be looking for exploratory opportunities that mimic the Bongor Basin's basement buried hills, which are currently the location of commercial oil production.

Influence of Genetic Ancestry on Gene-Environment Interactions of Polygenic Risk and Sociocultural Factors: Results from the Hispanic Community Health Study/Study of Latinos.

Many present analyses of Hispanic/Latino populations in epidemiologic research aggregate all members of this ethnic group, despite immense diversity in genetic backgrounds, environment, and culture between and across Hispanic/Latino background groups. Using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we examined the role of self-identified background group and genetic ancestry proportions in gene-environment interactions influencing the relationship between body mass index (BMI) and a polygenic score for BMI (PGS BMI ). Weighted univariate and multivariable generalized linear models were executed to compare the effects of environmental variables identified a priori by McArdle et al. 2021. Both Amerindigenous (AME) ancestry proportion and background group identity were statistically modeled as confounders both through stratified and joint analyses to understand their influence on the relationship between BMI and PGS BMI , while incorporating gene-environment interactions of PGS x diet and PGS x age-at-immigration. After complex survey weighting, 7,075 participants remained in the analytic sample, representing individuals of six background groups: Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American. The distributions of key environmental and sociocultural variables were heterogeneous between Hispanic/Latino background groups. Associations of these variables with AME ancestry were similarly heterogeneous upon stratification, indicating confounding by background group. In a predictive model for BMI incorporating health, immigration, and environmental variables, PGS BMI performance decreased with increasing AME ancestry proportion. In this model, most statistically significant GxE interactions lost significance after ancestry and background stratification, except for PGS x age-at-immigration interactions in some strata: Mexican background individuals born in the US compared to those >=21 years old at migration (β=1.33, p<0.01), Dominican background individuals 6-12 years old at migration compared to those >=21 years old at migration (β=4.38, p<0.001), and Cuban background individuals 0-5 years old at migration compared to those >=21 years old at migration (β=2.20, p=0.015), where US-born includes individuals born in the US 50 states/DC. Controlling for self-identified background group identity and genetic ancestry did not eliminate statistically significant differences in interactions between AME ancestry and environmental variables in certain strata of AME ancestry among some Hispanic/Latino background groups in HCHS/SOL.

XGBoost as a reliable machine learning tool for predicting ancestry using autosomal STR profiles - Proof of method

The aim of this study was to test the validity of a predictive model of ancestry affiliation based on Short Tandem Repeat (STR) profiles. Frequencies of 29 genetic markers from the Promega website for four distinct population groups (African Americans, Asians, Caucasians, Hispanic Americans) were used to generate 360,000 profiles (90000 profiles per group), which were later used to train and test a range of machine learning algorithms with the goal of establishing the most optimal model for accurate ancestry prediction. The chosen models (Decision Trees, Support Vector Machines, XGBoost, among others) were deployed in Python, and their performance was compared. The XGBoost model outperformed others, displaying significant predictive power with an accuracy rating of 94.24 % for all four classes, and an accuracy rating of 99.06 % on a differentiation task involving Asian, African American, and Caucasian subsamples and an accuracy rating of 98.57 % when differentiating between the African-American, Asian, and the mixed group combining Caucasians and Hispanics. Evaluating the impact of training set size revealed that model accuracy peaked at 94 % with 90,000 profiles per category, but decreased to 83 % as the number of profiles per category was reduced to 500, particularly affecting precision when distinguishing between Caucasian and Hispanic subgroups. The study further investigated the impact of marker quantity on model accuracy, finding that the use of 21 markers, commonly available in commercial amplification kits, resulted in an accuracy of 96.3 % for African Americans, Asians, and Caucasians, and 88.28 % for all four groups combined. These findings underscore the potential of STR-based models in forensic analysis and hint at the broader applicability of machine learning in genetic ancestry determination, with implications for enhancing the precision and reliability of forensic investigations, particularly in heterogeneous environments where ancestral background can be a crucial piece of information.

Long-read sequencing enables comprehensive molecular genetic diagnosis of Fabry disease

BackgroundThe clinical diagnosis of Fabry Disease (FD) can be challenging due to the clinical heterogeneity, especially in females. Patients with FD often experience a prolonged interval between the onset of symptoms and receiving a diagnosis. Genetic testing is the gold standard for precise diagnosis of FD, however conventional genetic testing could miss deep intronic variants and large deletions or duplications. Although next-generation sequencing, which analyzes numerous genes, has been successfully used for FD diagnosis and can detect complex variants, an effective and rapid tool for identifying a wide range of variants is imminent, contributing to decrease the diagnostic delay.MethodsThe comprehensive Analysis of FD (CAFD) assay was developed for FD genetic diagnosis, employing long-range PCR coupled with long-read sequencing to target the full-length GLA gene and its flanking regions. Its clinical performance was assessed through a comparative analysis with Sanger sequencing.ResultsGenetic testing was performed on 82 individuals, including 48 probands and 34 relatives. The CAFD assay additionally identified variants in two probands: one had a novel and de novo pathogenic variant with a 1715 bp insertion in intron 4, and the other carried two deep intronic VUS variants in cis-configuration also in intron 4. In total, CAFD identified 47 different variants among 48 probands. Of these, 42 (89.36%, 42/47) were pathogenic, while 5 (10.64%, 5/47) were VUS. Sixteen (34.04%, 16/47) of the variants were novel, including 15 SNV/Indels and one large intronic insertion. Pedigree analysis of 21 probands identified four de novo disease-causing variants. Hence, FD exhibits not only variable clinical presentations but also a wide spectrum of variants. Utilizing a comprehensive testing algorithm for diagnosing FD, which includes enzyme activity, clinical features, and genetic testing, the diagnostic yield of CAFD is 97.92% (47/48), which is higher than that of conventional Sanger sequencing, at 95.83% (46/48).ConclusionThe duration between initial clinical presentation and diagnosis remains long and winding. CAFD provides precise diagnosis for a wide spectrum of GLA variants, promoting timely diagnosis and appropriate treatment for FD patients.

Pedigree analysis of the Latvian Warmblood horse heavy type population

Pedigree analysis of the Latvian Warmblood horse heavy type population

Genetic Assessment of a Captive Population of Eurasian Stone-Curlew (Burhinus oedicnemus), Source for the Reinforcement of Wild Populations

Although ex situ conservation programs are increasingly valuable support tools for in situ conservation measures, success depends on these captive individuals to be genetically representative of the recipient population. The Eurasian stone-curlew (Burhinus oedicnemus) inhabit steppes that represent some of the most degraded and exploited habitats worldwide. A captive breeding program was implemented in Morocco as a pre-emptive effort for the conservation of the North African subspecies Burhinus oedicnemus saharae. However, the genetic origins of the founders of the captive flock were unknown. We applied a multi-locus approach to characterize the genetic ancestry of the current captive breeding flock by comparing it to wild populations from both Western and Eastern Morocco. Mitochondrial DNA and microsatellite markers were employed to assess levels of genetic diversity and relatedness within each sample, as well as potential genetic differentiation between wild and captive samples through PCA and admixture analyses. We recovered similar genetic diversity estimates, low levels of relatedness, and little differentiation between captive and wild samples. These results confirmed the Moroccan origin of the founders. We provide recommendations for the optimization of the Eurasian Stone Curlew conservation breeding program but also for future conservation breeding programs to ensure the effective conservation of genetic diversity and wild populations.

Severe toxicities in amazonian populations and the role of precision medicine in acute lymphoblastic leukemia treatment.

Corticosteroids, such as prednisone or dexamethasone, constitute integral components of antineoplastic regimens for Acute Lymphoblastic Leukemia (ALL) therapy, albeit accompanied by significant adverse effects. The multifactorial nature of interindividual variability in drug response, encompassing genetic polymorphisms, underscores the complexity of pharmacotherapy outcomes. However, pharmacogenetic investigations hitherto have predominantly focused on cohorts of European and North American descent, thus limiting the generalizability of findings to populations with minimal representation. Indigenous populations in Brazil, particularly those inhabiting the Amazon region, exhibit a distinctive genetic heritage, predominantly characterized by Native American ancestry. These populations frequently manifest suboptimal therapeutic responses and elevated mortality rates following ALL treatment. Therefore, delineating the molecular signatures of genes implicated in the corticosteroid pathway within these indigenous cohorts assumes paramount importance. This study identified novel variants within genes associated with the glucocorticoid pathway in indigenous Amazonian populations and conducted comparative analyses of variant frequencies across diverse global populations. The findings underscore the genetic uniqueness of indigenous groups and highlight the potential impact of genetic factors on adverse responses to ALL treatment. Precision medicine approaches tailored to the genetic peculiarities of indigenous populations emerge as imperative strategies for optimizing therapeutic efficacy and mitigating treatment-related toxicities in these communities.

A Multidisciplinary Approach for the Assessment of the Last Surviving ‘Marrone di Chiusa Pesio’ Chestnut Trees in the Piemonte Region (Italy)

Chestnut orchards are a multifunctional resource, providing not only fruit or wood but also playing a role in the conservation of mountain and hillside landscapes. In the Piemonte Region, Italy, a rich genetic heritage of chestnut genotypes has contributed to considerable biodiversity and environmental value. The study aimed to valorize an important example of the chestnut agrobiodiversity in the Piemonte Region by focusing on the ‘Marrone di Chiusa Pesio’ (MCP) cultivar (cv). A multidisciplinary approach was applied, involving genetic and morphological analyses, Visual Tree Assessment (VTA), and phytochemical and nutritional profiling. The plant census provided identification and geolocation of 187 MCP specimens; the 20 most representative trees were genetically analyzed, and then, through the VTA, their morpho-functional status was evaluated. The nutraceutical properties and phytochemical composition were assessed by measuring the total polyphenol content (TPC), antioxidant capacity (AOC), and other phytochemical classes through spectrophotometric and chromatographic methods. The results showed significantly higher TPC values (ranged from 36.51 ± 1.60 mgGAE/100 g of dried weight—DW to 103.14 ± 1.24 mgGAE/100 g DW) compared to other ‘Marrone-type’ cultivars, along with high levels of key phenolic markers, bioactive compounds, and nutritional substances. These included tannins (about 22–28 mg/100 g DW) and cinnamic acids (about 23–25 mg/100 g DW), followed by flavonols, benzoic acids, organic acids, monoterpenes, vitamin C, and catechins, listed in order of predominance. A Principal Component Analysis (PCA) was performed to observe the distribution of the samples and their correlations based on the chemical composition. The results confirmed the interesting phytochemical properties of the ‘Marrone di Chiusa Pesio’ nuts, together with their good morphological and functional properties. Given the ongoing genetic erosion of Castanea sativa cultivars, due to cultivation abandonment and climate change, the main factors contributing to the progressive loss of biodiversity worldwide, the presented approach aimed to provide an overview of the conservation status of the local agrobiodiversity. This study highlighted the value of a local chestnut cultivar, presenting the low conservation status of the few remaining specimens. The goal was to define the significant phenotypic variation regarding MCP in the considered area due to environmental variations, which may be of interest in its genetic adaptation to climate change. The study may potentially encourage the development of strategies for actively conserving the forest agrobiodiversity and hillside ecosystem services in the highly diverse landscapes of the Alpine valleys.

Private detection of relatives in forensic genomics using homomorphic encryption.

Forensic analysis heavily relies on DNA analysis techniques, notably autosomal Single Nucleotide Polymorphisms (SNPs), to expedite the identification of unknown suspects through genomic database searches. However, the uniqueness of an individual's genome sequence designates it as Personal Identifiable Information (PII), subjecting it to stringent privacy regulations that can impede data access and analysis, as well as restrict the parties allowed to handle the data. Homomorphic Encryption (HE) emerges as a promising solution, enabling the execution of complex functions on encrypted data without the need for decryption. HE not only permits the processing of PII as soon as it is collected and encrypted, such as at a crime scene, but also expands the potential for data processing by multiple entities and artificial intelligence services. This study introduces HE-based privacy-preserving methods for SNP DNA analysis, offering a means to compute kinship scores for a set of genome queries while meticulously preserving data privacy. We present three distinct approaches, including one unsupervised and two supervised methods, all of which demonstrated exceptional performance in the iDASH 2023 Track 1 competition. Our HE-based methods can rapidly predict 400 kinship scores from an encrypted database containing 2000 entries within seconds, capitalizing on advanced technologies like Intel AVX vector extensions, Intel HEXL, and Microsoft SEAL HE libraries. Crucially, all three methods achieve remarkable accuracy levels (ranging from 96% to 100%), as evaluated by the auROC score metric, while maintaining robust 128-bit security. These findings underscore the transformative potential of HE in both safeguarding genomic data privacy and streamlining precise DNA analysis. Results demonstrate that HE-based solutions can be computationally practical to protect genomic privacy during screening of candidate matches for further genealogy analysis in Forensic Genetic Genealogy (FGG).

A Functional Linear Regression for High‐Resolution 3D Faces

ABSTRACTMany scientific disciplines are faced with the challenge of extracting meaningful information from large, complex and highly structured datasets. A significant portion of contemporary statistical research is dedicated to developing tools for handling such data. This paper introduces a functional linear regression model specifically designed for 3D facial shapes, which are viewed as manifolds. We propose a comprehensive framework that includes converting 3D facial data into functional objects, employing a functional principal component analysis method and utilising a function‐on‐scalar regression model. This framework facilitates computation for high‐dimensional data and is employed to investigate how individual traits, such as age and genetic ancestry, impact the diversity of human facial features.

Difficult decisions and possible choices: Rare diseases, genetic inheritance and reproduction of the family

This article sets out to explore the dilemmas present in the reproductive practices of people affected by rare hereditary diseases, focusing on the use of diagnostic tests and the practice of genetic counselling in Brazil. The development of technologies capable of mapping ‘genetic flaws’ prior to conception or in prenatal consultations has led researchers to consider how these technologies may be shaping contemporary subjectivities related to kinship and guiding reproductive decisions based on knowledge of our ‘genetic heritage.’ Genetic counselling has emerged in this setting as a modality of health knowledge and information capable of assisting people, especially women, in their reproductive choices. In Brazil, access to these technologies and their use has proven to be unequal and heterogeneous. I argue that the idea of ‘choice’ that permeates genetic counselling needs to be problematized by considering the social, cultural, economic, affective and moral frameworks in which women are inserted and that inform and/or determine their reproductive decisions. Based on this premise, I analyse how families ‘at risk’ of rare hereditary diseases deal with the idea of ‘genetic inheritance’ in relation to the ‘wish to have children’, and the impasses surrounding the idea of ‘informed choice’ when we evaluate this rhetoric in the context of the shortfalls in access to healthcare and the limits to reproductive justice in Brazil.