Search

Estimates of the influence of inbreeding on the fitness of wild animals can guide genetic conservation in rare species. Conservation genetics is important in Mexican wolves (Canis lupus baileyi) because the current population descended from 7 founders and mean inbreeding is relatively high. As an endangered subspecies, Mexican wolves are actively managed using select conflict avoidance measures and by placing captive‐born foster pups into wild litters. We obtained data on inbreeding coefficients of wolf pups and adults based on a pedigree dating to 1957 and data on reproduction for wild wolf packs during 1998–2022. We estimated trends in inbreeding coefficients and the associations between dam, sire, and pup inbreeding coefficients and pup recruitment to age 9 months, and assessed 3 components of recruitment: probability of producing a litter, number of pups produced, and recruitment conditional on successful reproduction. We generated estimates using generalized linear mixed models and bootstrapped estimates of confidence intervals. Mean inbreeding coefficients were high (0.227, SD = 0.047) in the wild population, but we detected no significant evidence of an increase during 2010–2022. Overall, the net associations of dam, sire, and pup inbreeding coefficients with our primary fitness metric, pup recruitment to age 9 months, did not differ from zero. While high inbreeding coefficients are a concern for the long‐term recovery of the subspecies, the stable level of inbreeding, lack of evidence for inbreeding depression, high pup production (5.1 pups/litter, SD = 1.64), and rapid population growth (384% increase from 2010–2022) indicate that inbreeding has not prevented rapid progress towards recovery goals under current management practices. [ABSTRACT FROM AUTHOR]

Background: Common genetic variants with small effect sizes have been associated with rotator cuff tearing although very few rare, highly penetrant variants have been identified. The purpose of this pilot study was to identify dominant coding variants that segregated with affected individuals in pedigrees at high risk for rotator cuff tears (RCTs). We hypothesize that rare variants contribute to symptomatic RCTs and that they can be identified in related cases with a full-thickness tear requiring surgical management. Methods: We used the Utah Population Database to identify pedigrees that exhibited a significant excess of individuals who had undergone surgical repair of a full-thickness RCT. We analyzed whole exome sequence analysis to identify rare coding variants in 9 independent affected cousin pairs (first or second cousins) who had undergone arthroscopic surgery for repair of a full-thickness RCT (mean age at diagnosis 68 years). Validation of association of the candidate variants with risk for rotator cuff tearing was accomplished utilizing data from the UK Biobank and a separate cohort of unrelated cases of full-thickness RCTs. Results: A total of 82 rare (minor allele frequency

Sex-biased demography, including sex-biased survival or migration, can alter allele frequency changes across the genome. In particular, we can expect different patterns of genetic variation on autosomes and sex chromosomes due to sex-specific differences in life histories, as well as differences in effective population size, transmission modes, and the strength and mode of selection. Here, we demonstrate the role that sex differences in life history played in shaping short-term evolutionary dynamics across the genome. We used a 25-year pedigree and genomic dataset from a long-studied population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of sex-biased demography and inheritance in shaping genome-wide allele frequency trajectories. We used gene dropping simulations to estimate individual genetic contributions to future generations and to model drift and immigration on the known pedigree. We quantified differential expected genetic contributions of males and females over time, showing the impact of sex-biased dispersal in a monogamous system. Due to female-biased dispersal, more autosomal variation is introduced by female immigrants. However, due to male-biased transmission, more Z variation is introduced by male immigrants. Finally, we partitioned the proportion of variance in allele frequency change through time due to male and female contributions. Overall, most allele frequency change is due to variance in survival and births. Males and females make similar contributions to autosomal allele frequency change, but males make higher contributions to allele frequency change on the Z chromosome. Our work shows the importance of understanding sex-specific demographic processes in characterizing genome-wide allele frequency change in wild populations. [ABSTRACT FROM AUTHOR]

In a genetically admixed population, admixed individuals possess genealogical and genetic ancestry from multiple source groups. Under a mechanistic model of admixture, we study the number of distinct ancestors from the source populations that the admixture represents. Combining a mechanistic admixture model with a recombination model that describes the probability that a genealogical ancestor is a genetic ancestor, for a member of a genetically admixed population, we count genetic ancestors from the source populations—those genealogical ancestors from the source populations who contribute to the genome of the modern admixed individual. We compare patterns in the numbers of genealogical and genetic ancestors across the generations. To illustrate the enumeration of genetic ancestors from source populations in an admixed group, we apply the model to the African-American population, extending recent results on the numbers of African and European genealogical ancestors that contribute to the pedigree of an African-American chosen at random, so that we also evaluate the numbers of African and European genetic ancestors who contribute to random African-American genomes. The model suggests that the autosomal genome of a random African-American born in the interval 1960–1965 contains genetic contributions from a mean of 162 African (standard deviation 47, interquartile range 127–192) and 32 European ancestors (standard deviation 14, interquartile range 21–43). The enumeration of genetic ancestors can potentially be performed in other diploid species in which admixture and recombination models can be specified. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background Short tandem repeats (STRs) compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family. Results We use HipSTR to identify de novo STR mutations in the 2nd generation of these pedigrees and require transmission to the third generation for validation. Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10−5 mutations per locus per generation. Perfect repeats mutate about 2 × more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements. Conclusions Approximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants.

A central goal of population genetics is to understand how genetic drift, natural selection, and gene flow shape allele frequencies through time. However, the actual processes underlying these changes-variation in individual survival, reproductive success, and movement-are often difficult to quantify. Fully understanding these processes requires the population pedigree, the set of relationships among all individuals in the population through time. Here, we use extensive pedigree and genomic information from a long-studied natural population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of different evolutionary processes in shaping patterns of genetic variation through time. We performed gene dropping simulations to estimate individual genetic contributions to the population and model drift on the known pedigree. We found that observed allele frequency changes are generally well predicted by accounting for the different genetic contributions of founders. Our results show that the genetic contribution of recent immigrants is substantial, with some large allele frequency shifts that otherwise may have been attributed to selection actually due to gene flow. We identified a few SNPs under directional short-term selection after appropriately accounting for gene flow. Using models that account for changes in population size, we partitioned the proportion of variance in allele frequency change through time. Observed allele frequency changes are primarily due to variation in survival and reproductive success, with gene flow making a smaller contribution. This study provides one of the most complete descriptions of short-term evolutionary change in allele frequencies in a natural population to date.

Bipolar disorder (BD) is a debilitating neuropsychiatric disorder, which is associated with genetic variation through "vast but mixed" Genome-Wide Association Studies (GWAS). Transcriptome-Wide Association Study (TWAS) is more effective in explaining genetic factors that influence complex diseases and can help identifying risk genes more reliably. So, this study aims to identify potential BD risk genes in pedigrees with TWAS. We conducted a TWAS analysis with expression quantitative trait loci (eQTL) analysis on extended BD pedigrees, and the BD genome-wide association study (GWAS) summary data acquired from the Psychiatric Genomics Consortium (PGC). Furthermore, the BD-associated genes identified by TWAS were validated by mRNA expression profiles from the Gene Expression Omnibus (GEO) Datasets (GSE23848 and GSE46416). Functional enrichment and annotation analysis were implemented by RStudio (version 4.2.0). TWAS identified 362 genes with P value < 0.05, and 18 genes remain significant after Bonferroni correction, such as SEMA3G (P TWAS =1.07 × 10-11), ALOX5AP (P TWAS =3.12 × 10-8), and PLEC (P TWAS =1.27 × 10-7). Further 6 overlapped genes were detected in integrative analysis, such as UQCRB (P TWAS =0.0020, P mRNA =0.0000), TMPRSS9 (P TWAS =0.0405, P mRNA =0.0032), and SNX10 (P TWAS =0.0104, P mRNA =0.0015). Using genes identified by TWAS, Gene Ontology (GO) enrichment analysis identified 40 significant GO terms, such as mitochondrial ATP synthesis coupled electron transport, mitochondrial respiratory, aerobic electron transport chain, oxidative phosphorylation, mitochondrial membrane proteins, and ubiquinone activity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis identified significant 15 pathways for BD, such as Oxidative phosphorylation, endocannabinoids signaling, neurodegeneration, and reactive oxide species. We found a set of BD-associated genes and pathways, validating the important role of neurodevelopmental abnormalities, inflammatory responses, and mitochondrial dysfunction in the pathology of BD, offering novel information for comprehending the genetic basis of BD. [ABSTRACT FROM AUTHOR]

Purpose: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families., Methods: Including 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10,000 person-years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the study design, we primarily focused on cancer risk in women., Results: We found significant increased risks of colorectal cancer (CRC; SIR = 1.43, 95% CI = 1.14-1.76; AER = 1.43) and hematological cancers (SIR = 1.32; 95% CI = 1.02-1.67; AER = 0.87). CRC was significantly more frequent from age 45 onward., Conclusion: A significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well; however, further research is needed to determine who may profit from this additional colorectal surveillance., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The current hypothesis, along with the opinion of the breeders, is that a cat with two copies of the white spotting allele (SS) has white on more than half of its body, while a cat with only one copy (Ss) has white on less than half of its body. The present study was based on the analysis of two large pedigree databases of Siberian cats (23,905 individuals in PawPeds and 21,650 individuals in Felis Polonia database). The distribution of the amount of white spotting in the offspring of cats with different amounts of white was investigated. Significant differences compared to expected distributions were observed. In many cases the amount of white in cats that were supposed to be homozygous was less than 50% of the body, while in many supposedly heterozygous cats a very large amount of white (over 50%) was observed. This phenomenon was also presented on the verified examples of the specific families excluding possible errors in determining the amount of white by the breeder. The collected evidence suggests that there are other factors involved in the inheritance of the amount of white in cats and the current hypothesis should be revised. [ABSTRACT FROM AUTHOR]

Objective A family history of a chronic disease often predicts disease risk, with predictive value determined by heritability, the proportion of variation in risk explained by inherited genetic factors. Our objective was to assess the validity of disease heritability estimates from electronic healthcare records (EHRs) that capture family relationships and disease diagnoses. Approach A population-based investigation was conducted using healthcare records from Manitoba, Canada for 1970 to 2021. We constructed family relationships for up to four generations using health insurance registration information containing unique family and individual identifiers. Health histories for family members were created using diagnosis codes in hospital and physician visit records. Linear mixed-effects models were used to estimate heritability (h) for 130 chronic health conditions using open-source Clinical Classifications Software that defines clinically-meaningful disease categories. Comparisons between EHR-derived estimates and genetically-derived estimates from published studies were used to assess validity of the methodology. Results Health insurance registration data were used to construct 10,000 families that included 116,879 individuals. Median family size was 9 (interquartile range: 8). Median observation time was 39.6 years (interquartile range: 25.7). Males comprised half (51.0%) of family members. A total of 272,114 familial relationships were identified; slightly more than half (53%) were first degree (i.e., child and parent) relationships. One-third (33.2%) of families were comprised of four generations; only 15.3% were comprised of two generations. Heritability estimates were consistent with published genetically-derived estimates for several conditions, including diabetes (EHR h = 0.29 vs. 0.22), anemia (EHR h = 0.21 vs. 0.20), and asthma (EHR h = 0.34 vs. 0.33). However, inconsistencies were identified for pancreatic disorders, gastrointestinal conditions, some mental health conditions, and heart disease. Conclusion EHRs provide a promising approach to explore heritability of selected health conditions in large, diverse populations. Inconsistencies between EHR-derived and genetically-derived estimates are indicative of the limitations of diagnoses recorded for administrative purposes. Future research will explore sex-specific heritability estimates and effects of change in disease diagnosis coding over time.

We examined the rate and nature of mitochondrial DNA (mtDNA) mutations in humans using sequence data from 64,806 contemporary Icelanders from 2,548 matrilines. Based on 116,663 mother-child transmissions, 8,199 mutations were detected, providing robust rate estimates by nucleotide type, functional impact, position, and different alleles at the same position. We thoroughly document the true extent of hypermutability in mtDNA, mainly affecting the control region but also some coding-region variants. The results reveal the impact of negative selection on viable deleterious mutations, including rapidly mutating disease-associated 3243A>G and 1555A>G and pre-natal selection that most likely occurs during the development of oocytes. Finally, we show that the fate of new mutations is determined by a drastic germline bottleneck, amounting to an average of 3 mtDNA units effectively transmitted from mother to child. [Display omitted] • Detection of 8,199 mutations in 116,663 mother-child mtDNA transmissions • Position and allele-specific mutation rates reveal asymmetric hypermutability • Evidence for both pre- and post-natal selection against mtDNA variants • Children inherit effectively only ∼3 units of mtDNA from their mothers This large-scale pedigree study of human mtDNA mutations reveals substantial selection against deleterious variants both before and after birth, characterizes extensive differences in mutability by position and allele, and shows that children only inherit around 3 units of mtDNA from their mothers. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Babylon Center for Humanities Studies is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To clinically characterize patients and family members with cleft lip and/or palate (CL/P) and associated congenital malformations or syndromes and propose possible inheritance patterns. Materials and methods: An observational study of patients with CL/P, including medical and family history and intra- and extra-oral examination of their family members, was performed. Results: Two hundred sixty-six patients, 1257 family members, and 42 pedigrees were included in the study. The distribution of patients according to the cleft type was 57.9% with CLP, 25.2% with cleft palate (CPO), and 12.8% with cleft lip with/without alveolus (CL/A). Seventy-four (27.8%) patients had associated malformations, and 24 (9.2%) a syndrome. The skeletal (27.7%), cardiovascular (19.3%) systems, and eyes (22.9%) were most commonly affected. Pierre Robin Sequence (7 patients) and van der Woude (4) were the most common syndromes. The majority of patients with CPO (19/24) had an associate syndrome. The families had an average of 2.45 affected members. Conclusion: Individual and interfamilial phenotypic variability in patients with CL/P makes the understanding of etiopathogenesis challenging. Clinical relevance: The overall prevalence of individuals with CL/P and their pedigrees with associated malformations and syndromes emphasize the need for early identification, interdisciplinary, and long-term planning. [ABSTRACT FROM AUTHOR]

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning.

Attention deficit hyperactivity disorder (ADHD) is associated with substantial functional impairment in children and in adults. Many individuals with ADHD have clear neurocognitive deficits, including problems with visual attention, processing speed, and set shifting. ADHD is etiologically complex, and although genetic factors play a role in its development, much of the genetic contribution to ADHD remains unidentified. We conducted clinical and neuropsychological assessments of 294 individuals (269 with ADHD) from 163 families (48 multigenerational families created using genealogical reconstruction, 78 affected sib pair families, and 37 trios) from the Central Valley of Costa Rica (CVCR). We used principal components analysis (PCA) to group neurocognitive and behavioral variables using the subscales of the Child Behavior Checklist (CBCL) and 15 neuropsychological measures, and created quantitative traits for heritability analyses. We identified seven cognitive and two behavioral domains. Individuals with ADHD were significantly more impaired than their unaffected siblings on most behavioral and cognitive domains. The verbal IQ domain had the highest heritability (92%), followed by auditory attention (87%), visual processing speed and problem solving (85%), and externalizing symptoms (81%). The quantitative traits identified here have high heritabilities, similar to the reported heritability of ADHD (70-90%), and may represent appropriate alternative phenotypes for genetic studies. The use of multigenerational families from a genetically isolated population may facilitate the identification of ADHD risk genes in the face of phenotypic and genetic heterogeneity.

Classic Mendelian inheritance is the bedrock of population genetics and underpins pedigree‐based management of animal populations. However, assumptions of Mendelian inheritance might not be upheld in conservation breeding programmes if early viability selection occurs, even when efforts are made to equalise genetic contributions of breeders. To test this possibility, we investigated deviations from Mendelian proportions in a captive metapopulation of the endangered Tasmanian devil. This marsupial population is ideal for addressing evolutionary questions in conservation due to its large size, range of enclosure types (varying in environmental conditions), good genomic resources (which aid interpretation), and the species' biology. Devil mothers give birth to more offspring than they can nurse in the pouch, providing the potential for intense viability selection amongst embryos. We used data from 140 known sire‐dam‐offspring triads to isolate within‐family selection from population‐level mechanisms (such as mate choice or inbreeding), and compared observed offspring genotypes at 123 targeted SNPs to neutral (i.e., Mendelian) expectations. We found lower offspring heterozygosity than expected, and subtle patterns that varied across a gradient of management intensity from zoo‐like enclosures to semi‐wild environments for some loci. Meiotic drive or maternal‐foetal incompatibilities are consistent with our results, although we cannot statistically confirm these mechanisms. We found some evidence that maternal genotype affects annual litter size, suggesting that family‐level patterns are driven by differential offspring mortality before birth or during early development. Our results show that deviations from Mendelian inheritance can occur in conservation programmes, despite best‐practice management to prevent selection. [ABSTRACT FROM AUTHOR]

Statistical genetics is undergoing the same transition to big data that all branches of applied statistics are experiencing. With the advent of inexpensive DNA sequencing, the transition is only accelerating. This brief review highlights some modern techniques with recent successes in statistical genetics. These include: (a) lasso penalized regression and association mapping, (b) ethnic admixture estimation, (c) matrix completion for genotype and sequence data, (d) the fused lasso and copy number variation, (e) haplotyping, (f) estimation of relatedness, (g) variance components models, and (h) rare variant testing. For more than a century, genetics has been both a driver and beneficiary of statistical theory and practice. This symbiotic relationship will persist for the foreseeable future.

Low penetrance of Parkinson's disease (PD) associated with GBA pathogenic variants indicates the presence of modifiers genes. Clusters of PD cases in certain families with GBA variants would serve as a strong evidence for the clinical relevance of such modifiers. We studied eight family trees of non-Parkinsonian, GBA-N370S homozygote, Gaucher probands, with multiple cases of PD. Differences in PD risk associated with different GBA variants were balanced by variant homozygosity. In these families, all PD cases stemmed from only one of the proband's parents. This observation provides a direct epidemiological evidence for genetic modifiers determining PD risk in GBA variant carriers. [ABSTRACT FROM AUTHOR]

Background: Common genetic variants with small effect sizes have been associated with rotator cuff tearing although very few rare, highly penetrant variants have been identified. The purpose of this pilot study was to identify dominant coding variants that segregated with affected individuals in pedigrees at high risk for rotator cuff tears (RCTs). We hypothesize that rare variants contribute to symptomatic RCTs and that they can be identified in related cases with a full-thickness tear requiring surgical management., Methods: We used the Utah Population Database to identify pedigrees that exhibited a significant excess of individuals who had undergone surgical repair of a full-thickness RCT. We analyzed whole exome sequence analysis to identify rare coding variants in 9 independent affected cousin pairs (first or second cousins) who had undergone arthroscopic surgery for repair of a full-thickness RCT (mean age at diagnosis 68 years). Validation of association of the candidate variants with risk for rotator cuff tearing was accomplished utilizing data from the UK Biobank and a separate cohort of unrelated cases of full-thickness RCTs., Results: A total of 82 rare (minor allele frequency <0.005) coding variants were identified as shared in at least one cousin pair affected with full-thickness rotator cuff tearing belonging to a high-risk pedigree, which included variants in RUNX1, ADAM12 , TGFBR2 , APBB1 , PDLIM7, LTBP1 , MAP3K4, and MAP3K1 . Analysis of 39 of these variants with data available in the UK Biobank (3899 cases with rotator cuff injury and 11,697 matched controls; mean case age 59.9 years) identified a significant association with the APBB1 gene (OR = 2.37, P  = .007, uncorrected). The PDLIM7 allele was found to be in significant excess in RCT cases in a separate cohort of Utah patients with full-thickness RCTs (10 carriers out of 458 independent, unrelated patients; minor allele frequency of 0.022) compared to a minor allele frequency of 0.0058 for the European (non-Finnish) control population rate (749 carriers out of 128612 tested) (chi-square test: 19.3 [ P  < .001])., Discussion: The analysis of closely related individuals with confirmed full-thickness RCTs from high-risk pedigrees has identified 82 rare, shared candidate genetic predisposition coding variants. Association of the PDLIM7 allele with risk for tear was confirmed in an independent cohort of RCTs. Further analysis of the variant alleles is required for confirmation of these genes in rotator cuff tearing., (© 2024 The Authors.)

The domesticated grapevine spread along the Mediterranean basin from the primary Near East domestication area, where the greatest genetic diversity is found in its ancestor, the wild vine populations. Portuguese wild populations are on the southwestern fringe of the distribution of the Vitis vinifera L. ssp. sylvestris (C.C. Gmel.) Hegi in Europe. During the last Glacial Period they became isolated from the previous continuum that had been the territory of wild vine populations. Archaeological remains of domesticated vinifera grapevines in Portugal date back from 795 Before Common Era (BCE) in the lower Tagus river basin. In this work, 258 Portuguese vinifera varieties and sylvestris plants were characterized using 261 single nucleotide polymorphism (SNP) markers. The study of the genetic diversity of this local germplasm, its population structure and kinship, all framed in their historical and geographical backgrounds, revealed a complex network of first-degree relationships, where only Iberian varieties are involved. Some Iberian genotypes, like Alfrocheiro (Bruñal, in Spain), Sarigo (Cayetana Blanca), Mourisco Branco (Hebén), Amaral (Caiño Bravo), and Marufo (Moravia Dulce) are ancestors of a considerable fraction of all the autochthonous analyzed varieties. A part of the diversity developed was mostly local in some cases as shown by the closeness of several varieties (Vinhos Verdes) to the wild cluster in different analyses. Besides, several evidences of introgression of domesticated germplasm into wild vines was found, substantiating the high risk of genetic contamination of the sylvestris subspecies. All these findings together to the known matching between the wild maternal lineage of the Iberian Peninsula and an important number of Portuguese grapevine varieties (chlorotype A), point out that some of these varieties derive, directly or indirectly, from originally local wild populations, supporting the possible occurrence of secondary events of local domestication, or, at least, of an introgression process of wild into cultivated grapevines.

Reproductive conflicts are expected in societies where nonbreeding helpers retain the ability to produce offspring. Despite potential competition from reproductively capable nestmates in social wasps, egg laying tends to be monopolised by a single or relatively few queens. Genetic studies on reproductive partitioning in Polistes paper wasps suggest high reproductive skew in the genus. Conflict is thought to be minimal due to nestmate relatedness or the possibility of inheriting a reproductive monopoly on a nest; consequently, there are inclusive fitness opportunities for nonreproductive helpers. However, most studies are limited to temperate wasp species. Given the cosmopolitan distribution of Polistes, genetic data on group conflicts are required for a broader range of tropical species to determine whether these trends apply across climatic zones. We examined female reproductive skew in the Neotropical paper wasp Polistes lanio, genotyping a selection of adults and pupae from established post-emergence nests using single-nucleotide polymorphisms (SNPs). SNP-based pedigree analyses indicate a reproductive monopoly held by a single queen, with queen replacement from natal nestmates and evidence of possible multiple mating. Relatedness between pupal offspring was high (r = 0.71). It is likely that high reproductive skew among females is a founding trait of Polistes societies, conserved among species that have spread into new environments from Indomalayan origins. [ABSTRACT FROM AUTHOR]

The domesticated grapevine spread along the Mediterranean basin from the primary Near East domestication area, where the greatest genetic diversity is found in its ancestor, the wild vine populations. Portuguese wild populations are on the southwestern fringe of the distribution of the Vitis vinifera L. ssp. sylvestris (C.C. Gmel.) Hegi in Europe. During the last Glacial Period they became isolated from the previous continuum that had been the territory of wild vine populations. Archaeological remains of domesticated vinifera grapevines in Portugal date back from 795 Before Common Era (BCE) in the lower Tagus river basin. In this work, 258 Portuguese vinifera varieties and sylvestris plants were characterized using 261 single nucleotide polymorphism (SNP) markers. The study of the genetic diversity of this local germplasm, its population structure and kinship, all framed in their historical and geographical backgrounds, revealed a complex network of first-degree relationships, where only Iberian varieties are involved. Some Iberian genotypes, like Alfrocheiro (Bruñal, in Spain), Sarigo (Cayetana Blanca), Mourisco Branco (Hebén), Amaral (Caiño Bravo), and Marufo (Moravia Dulce) are ancestors of a considerable fraction of all the autochthonous analyzed varieties. A part of the diversity developed was mostly local in some cases as shown by the closeness of several varieties (Vinhos Verdes) to the wild cluster in different analyses. Besides, several evidences of introgression of domesticated germplasm into wild vines was found, substantiating the high risk of genetic contamination of the sylvestris subspecies. All these findings together to the known matching between the wild maternal lineage of the Iberian Peninsula and an important number of Portuguese grapevine varieties (chlorotype A), point out that some of these varieties derive, directly or indirectly, from originally local wild populations, supporting the possible occurrence of secondary events of local domestication, or, at least, of an introgression process of wild into cultivated grapevines. [ABSTRACT FROM AUTHOR]

Affymetrix’s SNP (single nucleotide polymorphism) genotyping chips have increased the scope and decreased the cost of gene mapping studies. Because each SNP is queried by mul- tiple DNA probes, the chips present interesting challenges in genotype calling. Traditional clustering methods distinguish the three genotypes of a SNP fairly well given a large enough sample of unrelated individuals or a training sample of known genotypes. The present pa- per describes our attempt to improve genotype calling by constructing Gaussian penetrance models with empirically derived priors. The priors stabilize parameter estimation and borrow information collectively gathered on tens of thousands of SNPs. When data from related family members are available, Gaussian penetrance models capture the correlations in signals between relatives. With these advantages in mind, we apply the models to Affymetrix probe intensity data on 10,000 SNPs gathered on 63 genotyped individuals spread over eight pedigrees. We integrate the genotype calling model with pedigree analysis and examine a sequence of sym- metry hypotheses involving the correlated probe signals. The symmetry hypotheses raise novel mathematical issues of parameterization. Using the BIC criterion, we select the best combi- nation of symmetry assumptions. Compared to the genotype calling results obtained from Affymetrix’s software, we are able to reduce the number of no-calls substantially and quan- tify the level of confidence in all calls. Once pedigree analysis software can accommodate soft penetrances, we can expect to see more reliable association and linkage studies with less wasted genotyping data.

Analysing the impact of anthropogenic and natural river barriers on the dispersal of aquatic and semi‐aquatic species may be critical for their conservation. Knowledge of kinship relationships between individuals and reconstructions of pedigrees obtained using genomic data can be extremely useful, not only for studying the social organization of animals, but also inferring contemporary dispersal and quantifying the effect of specific barriers on current connectivity. In this study, we used kinship data to analyse connectivity patterns in a small semi‐aquatic mammal, the Pyrenean desman (Galemys pyrenaicus), in an area comprising two river systems with close headwaters and dams of various heights and types. Using a large SNP dataset from 70 specimens, we obtained kinship categories and reconstructed pedigrees. To quantify the barrier effect of specific obstacles, we built kinship networks and devised a method based on the assortativity coefficient, which measures the proportion between observed and expected kinship relationships across a barrier. The estimation of this parameter enabled us to infer that the most important barrier in the area was the watershed divide between the rivers, followed by a dam on one of the rivers. Other barriers did not significantly reduce the expected number of kinship relationships across them. This strategy and the information obtained with it may be crucial in determining the most important connectivity problems in an area and help develop conservation plans aimed at improving genetic exchange between populations of threatened species. see also the Perspective by Carroll and Gaggiotti [ABSTRACT FROM AUTHOR]

A central goal of population genetics is to understand how genetic drift, natural selection, and gene flow shape allele frequencies through time. However, the actual processes underlying these changes--variation in individual survival, reproductive success, and movement--are often difficult to quantify. Fully understanding these processes requires the population pedigree, the set of relationships among all individuals in the population through time. Here, we use extensive pedigree and genomic information from a long-studied natural population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of different evolutionary processes in shaping patterns of genetic variation through time. We performed gene dropping simulations to estimate individual genetic contributions to the population and model drift on the known pedigree. We found that observed allele frequency changes are generally well predicted by accounting for the different genetic contributions of founders. Our results show that the genetic contribution of recent immigrants is substantial, with some large allele frequency shifts that otherwise may have been attributed to selection actually due to gene flow. We identified a few SNPs under directional short-term selection after appropriately accounting for gene flow. Using models that account for changes in population size, we partitioned the proportion of variance in allele frequency change through time. Observed allele frequency changes are primarily due to variation in survival and reproductive success, with gene flow making a smaller contribution. This study provides one of the most complete descriptions of short-term evolutionary change in allele frequencies in a natural population to date. [ABSTRACT FROM AUTHOR]

Highlights • Cd induced pedigree-specific responses of antioxidant enzymes in clams. • Differential proteomic responses were induced in White and Zebra clams exposed to Cd. • The alterations of antioxidant enzymes were consistent with proteomic responses. • The pedigree of animal should be considered in ecotoxicology. Abstract Due to the industrial discharges, cadmium (Cd) has been one of typical heavy metal pollutants in the Bohai Sea. Manila clam Ruditapes philippinarum is frequently used for pollution biomonitoring and consists of several pedigrees, of which White and Zebra clams are the dominant pedigrees along the Bohai Sea coast. However, limited attention has been paid on the differential biological effects in different pedigrees of clam to heavy metals. In this work, the proteome profiling analysis was performed to reveal the differential proteomic responses in White and Zebra clams to Cd exposure (200 μg/L) for 48 h, followed by bioinformatical analysis. The proteomic investigations showed that Cd treatment induced more differentially expressed proteins (DEPs) in White clam samples than in Zebra clam samples. Based on the DEPs, we found that some key biological processes consisting of immune response and metabolism were commonly induced in both two pedigrees of clam. Uniquely, some processes related to cellular signaling, proteolysis and energy production were enhanced in Cd-treated White clam samples. Comparatively, the depletion in some unique processes on proteolysis and energy production was elicited in Cd-treated Zebra clam samples, as well as disorder in gene expression. Moreover, Cd exposure caused increases in CAT and POD activities in White clam samples and decreases in SOD and CAT activities in Zebra clams samples, which were consistent with the proteomic responses. Overall, these findings confirmed the differential biological effects of White and Zebra clams to Cd treatment, suggesting that the pedigree of animal should be taken into consideration in ecotoxicology studies. [ABSTRACT FROM AUTHOR]

A growing number of researchers suggest that female homosexuality is at least in part influenced by genetic factors. Unlike for male homosexuality, few familial studies have attempted to explore maintenance of this apparently fitness-detrimental trait in the population. Using multiple recruitment methods, we explored fecundity and sexual orientation within the pedigrees of 1,458 adult female respondents. We compared 487 homosexual and 163 bisexual with 808 heterosexual females and 30,203 of their relatives. Our data suggest that the direct fitness of homosexual females is four times lower than the direct fitness of heterosexual females of corresponding ages. The prevalence of nonheterosexuality within the homosexual female respondents’ families (2.83%) appear to be more than four times higher than the basal prevalence in the Italian population (0.63%). Pedigree size and relative fecundity in both the paternal and maternal sides of the homosexual women’s families were significantly higher than in the heterosexuals’ families. If confirmed, the relative average fecundity increase within the family seems to offset the loss in fitness due to the low direct fitness of homosexual females. Therefore, the balanced fecundity in the homosexual females’ families may allow the trait to be maintained at a low-frequency equilibrium in the population. [ABSTRACT FROM AUTHOR]

Objective: We analyze data sets consisting of pedigrees with age at onset of colorectal cancer (CRC) as phenotype. The occurrence of familial clusters of CRC suggests the existence of a latent, inheritable risk factor. We aimed to compute the probability of a family possessing this risk factor as well as the hazard rate increase for these risk factor carriers. Due to the inheritability of this risk factor, the estimation necessitates a costly marginalization of the likelihood. Methods: We propose an improved EM algorithm by applying factor graphs and the sum-product algorithm in the E-step. This reduces the computational complexity from exponential to linear in the number of family members. Results: Our algorithm is as precise as a direct likelihood maximization in a simulation study and a real family study on CRC risk. For 250 simulated families of size 19 and 21, the runtime of our algorithm is faster by a factor of 4 and 29, respectively. On the largest family (23 members) in the real data, our algorithm is 6 times faster. Conclusion: We introduce a flexible and run-time-efficient tool for statistical inference in biomedical event data with latent variables that opens the door for advanced analyses of pedigree data. [ABSTRACT FROM AUTHOR]

Reliable pedigree information facilitates a scientific approach to breeding, but errors can be introduced in many stages of a breeding program. Our objective was to use single nucleotide polymorphisms (SNPs) to check the pedigree records of elite North American potato germplasm. A population of 719 tetraploids was genotyped with an Infinium SNP array, yielding 5063 high-quality markers. Based on pedigree records, the dataset contained 198 parent-offspring trios, of which 182 were consistent with the marker data. For 13 of the 16 trios with a pedigree error, the true parent was identified in the population. By comparing the additive relationship matrix calculated from pedigree with the genetic distance calculated from markers, an additional 24 pedigree modifications were proposed, including the paternity of several varieties developed with bulk pollen. To ensure accurate pedigree records are published in the future, we recommend that new varieties be SNP genotyped and checked against this dataset. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the genetic basis, the coefficient of kinship, and the genetic diversity of rice varieties released between 2003 and 2014, in thirteen member countries of the Latin America Fund for Irrigated Rice (FLAR). Pedigrees of o 51 rice varieties were analyzed at the International Center for Tropical Agriculture (CIAT), Palmira, Colombia between 2014-2015 The genetic variability of these varieties was represented by 120 ancestral or traditional cultivars (2.4 ancestral/variety); 33 of these contributed to the 83.9% of their genes, from which, three (ancestors with IR 8 origin), accounted for 35.6% of their genes. It was also shown that the coefficient of kinship (rxy) between different commercial varieties ranged from 0.03 (very unrelated), up to 0.99 (highly related). The average rxy of all 51 varieties was = 0.19. Regarding the varieties by country, the average rxy varied, the minimum was obtained by Ecuador 0.13 and the varieties from Venezuela obtained the maximum 0.31. The cluster analysis separated the genotypes in fourteen different groups based on highly related or very unrelated varieties. These results indicate that a broadening of the genetic base has been accomplished. [ABSTRACT FROM AUTHOR]

In this study, a data set of 1140 progenies from 19 families that were composed of 13 half-sib and six full-sib families was used in the estimation of the genetic parameters of weight for juvenile turbot at 100 days post hatch. Sixty progenies were randomly selected from each family, and 20 of these individuals were genotyped at 12 microsatellite loci. Two sorts of relatedness, including pedigree relatedness ( PR) from a complete pedigree and average molecular relatedness ( AMR) from molecular markers, were compared to explore the feasibility of AMR in selective breeding when only parents were known. Two different animal models, Model 1 and Model 2 which were without and with the addition of maternal and common environmental effects, respectively, were used to estimate the variance component and breeding values for weight using restricted maximum likelihood ( REML) method. Thereafter, cross-validation was applied to investigate predictive ability of model and accuracy of breeding values. Pearson correlation analysis showed that AMR was highly correlated (0.91) with PR. According to conditional Akaike Information Criterion, the best models for AMR and PR methods were Model 2 and Model 1 respectively. Heritability estimates from AMR and PR methods based on their best models were 0.19 (±0.06) and 0.66 (±0.17). Cross-validation showed that AMR was comparable to PR in terms of predictive abilities and accuracies of breeding values based on the same model. This study therefore suggests that the AMR can be applied as alternative of PR when only parents were known. [ABSTRACT FROM AUTHOR]

Background: A number of large genomic datasets are being generated for studies of human ancestry and diseases. The ADMIXTURE program is commonly used to infer individual ancestry from genomic data. Results: We describe two improvements to the ADMIXTURE software. The first enables ADMIXTURE to infer ancestry for a new set of individuals using cluster allele frequencies from a reference set of individuals. Using data from the 1000 Genomes Project, we show that this allows ADMIXTURE to infer ancestry for 10,920 individuals in a few hours (a 5x speedup). This mode also allows ADMIXTURE to correctly estimate individual ancestry and allele frequencies from a set of related individuals. The second modification allows ADMIXTURE to correctly handle X-chromosome (and other haploid) data from both males and females. We demonstrate increased power to detect sex-biased admixture in African-American individuals from the 1000 Genomes project using this extension. Conclusions: These modifications make ADMIXTURE more efficient and versatile, allowing users to extract more information from large genomic datasets. [ABSTRACT FROM AUTHOR]

Background: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes.Methods: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually or as a group across an entire gene for association to aging phenotypes using family based tests.Results: We found significant associations to three genes and nine single variants. Most notably, we found a novel variant significantly associated with exceptional survival in the 3' UTR OBFC1 in 13 individuals from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL).Conclusions: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants. [ABSTRACT FROM AUTHOR]

Motivation: RVPedigree (Rare Variant association tests in Pedigrees) implements a suite of programs facilitating genome-wide analysis of association between a quantitative trait and autosomal region-based genetic variation. The main features here are the ability to appropriately test for association of rare variants with non-normally distributed quantitative traits, and also to appropriately adjust for related individuals, either from families or from population structure and cryptic relatedness.Implementation: RVPedigree is available as an R package.General Features: The package includes calculation of kinship matrices, various options for coping with non-normality, three different ways of estimating statistical significance incorporating triaging to enable efficient use of the most computationally-intensive calculations, and a parallelization option for genome-wide analysis.Availability: The software is available from the Comprehensive R Archive Network [CRAN.R-project.org] under the name 'RVPedigree' and at [https://github.com/GreenwoodLab]. It has been published under General Public License (GPL) version 3 or newer. [ABSTRACT FROM AUTHOR]

Family pedigrees allow for a more thorough understanding of human genetic disorders. They are used to help establish patterns of inheritance and to identify individuals at risk of disease. Pedigree analysis can be helpful in identifying genetic disorders that demonstrate mechanisms such autosomal dominant or recessive inheritance, X-linked inheritance, and anticipation., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The expected time to the most recent common ancestor (MRCA) of two alleles in a diploid individual is 4 N + 2 under random mating with a Poisson progeny distribution, but 8 N − 2 under maximum avoidance of inbreeding, which entails two progeny per mating pair. ( N is the number of mating pairs, hence 2 N is the number of individuals, hence 4 N is the number of alleles.) The interrelationship of inbreeding constraints and offspring distribution is investigated by varying the level of sib mating: prohibiting sib mating increases the time to MRCA by four generations and decreases the variance of the offspring distribution by 2 / N . With two progeny per mating pair, the expected time to the MRCA is 8 N − 2 under both random mating and sib mating prohibited, as well as under maximum avoidance of inbreeding, but this result does not hold for all mating structures with two progeny per mating pair. [ABSTRACT FROM AUTHOR]