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G3 (Bethesda, Md.) Feb 2023This paper proposes a solution to a long-standing problem concerning the joint distribution of allelic identity by descent between two individuals at two linked loci....
This paper proposes a solution to a long-standing problem concerning the joint distribution of allelic identity by descent between two individuals at two linked loci. Such distributions have important applications across various fields of genetics, and detailed formulas for selected relationships appear scattered throughout the literature. However, these results were obtained essentially by brute force, with no efficient method available for general pedigrees. The recursive algorithm described in this paper, and its implementation in R, allow efficient calculation of two-locus identity coefficients in any pedigree. As a result, many existing procedures and techniques may, for the first time, be applied to complex and inbred relationships. Two such applications are discussed, concerning the expected likelihood ratio in forensic kinship testing, and variances in realized relatedness.
Topics: Humans; Pedigree; Algorithms; Alleles; Models, Genetic
PubMed: 36525359
DOI: 10.1093/g3journal/jkac326 -
IEEE/ACM Transactions on Computational... 2018Reconstruction of ancestral relationships among genera, species, and populations is a core task in evolutionary biology. At the population level, pedigrees have been...
Reconstruction of ancestral relationships among genera, species, and populations is a core task in evolutionary biology. At the population level, pedigrees have been commonly used. Reconstruction of pedigree is required in practice due to legal or medical reasons. Pedigrees are very important to geneticists for inferring haplotype segments, recombination, and allele sharing status with which disease loci can be identified. Evaluating reconstruction methods requires comparing the inferred pedigree and the known pedigrees. Moreover, comparison of pedigrees is required in studying relationships among crops such as maize, wheat and barley, etc. In this paper, we discuss three models for comparison of pedigrees, the maximum pedigree isomorphism problem, the maximum paternal-path-preserved mapping problem, and the minimum edge-cutting mapping problem. For the maximum pedigree isomorphism problem, we prove that the problem is NP-hard and give a fixed-parameter algorithm for the problem. For the maximum paternal-path-preserved mapping problem, we give a dynamic-programming algorithm to find the mapping that preserves the maximum number of paternal paths between the two input pedigrees. For the minimum edge-cutting mapping problem, we prove that the problem is NP-hard and give a fixed-parameter algorithm with running time , where is the number of vertices in the two input pedigrees and is the number of edges to be cut. This algorithm is useful in practice when comparing two similar pedigrees.
Topics: Algorithms; Animals; Computational Biology; Computer Simulation; Female; Male; Models, Genetic; Pedigree
PubMed: 27076461
DOI: 10.1109/TCBB.2016.2550434 -
JAMA Dermatology Apr 2024
Topics: Humans; Keratoderma, Palmoplantar; Pedigree
PubMed: 38477895
DOI: 10.1001/jamadermatol.2024.0117 -
BMC Bioinformatics Dec 2020Pedigree files are ubiquitously used within bioinformatics and genetics studies to convey critical information about relatedness, sex and affected status of study...
BACKGROUND
Pedigree files are ubiquitously used within bioinformatics and genetics studies to convey critical information about relatedness, sex and affected status of study samples. While the text based format of ped files is efficient for computational methods, it is not immediately intuitive to a bioinformatician or geneticist trying to understand family structures, many of which encode the affected status of individuals across multiple generations. The visualization of pedigrees into connected nodes with descriptive shapes and shading provides a far more interpretable format to recognize visual patterns and intuit family structures. Despite these advantages of a visual pedigree, it remains difficult to quickly and accurately visualize a pedigree given a pedigree text file.
RESULTS
Here we describe ped_draw a command line and web tool as a simple and easy solution to pedigree visualization. Ped_draw is capable of drawing complex multi-generational pedigrees and conforms to the accepted standards for depicting pedigrees visually. The command line tool can be used as a simple one liner command, utilizing graphviz to generate an image file. The web tool, https://peddraw.github.io , allows the user to either: paste a pedigree file, type to construct a pedigree file in the text box or upload a pedigree file. Users can save the generated image file in various formats.
CONCLUSIONS
We believe ped_draw is a useful pedigree drawing tool that improves on current methods due to its ease of use and approachability. Ped_draw allows users with various levels of expertise to quickly and easily visualize pedigrees.
Topics: Computational Biology; Humans; Pedigree; Software
PubMed: 33297934
DOI: 10.1186/s12859-020-03917-4 -
European Journal of Pediatrics Jan 2016Decline and resurgence of breastfeeding (BF) characterized last century. Several factors influencing BF outcome were identified. Despite the huge literature on BF, no...
UNLABELLED
Decline and resurgence of breastfeeding (BF) characterized last century. Several factors influencing BF outcome were identified. Despite the huge literature on BF, no data on its matrilineal transmission are available. BF practice was prospectively followed in 2546 Italian mothers. Lactation and BF outcome were related, besides to known factors interfering with BF, to the occurrence of previous maternal and paternal BF. Recalls of grandmaternal and grand-grandmaternal BF behaviours allowed the construction of familiar pedigrees of BF across three generations. Having been breastfed was the strongest factor addressing successful BF establishment (odds ratio (OR) 9.33; 95% confidence interval (CI) 7.40-11.84; p < 0.0001) and BF duration (at 6 months: OR 3.79; 95% CI 3.11-4.64; p < 0.0001). The hazard ratio for breastfed vs non-breastfed mothers was 0.46 (95% CI 0.41-0.50; log-rank p < 0.0001). The rate of BF failures was fivefold higher in non-breastfed mothers, mostly occurring during lactogenesis when the let-down reflex becomes essential.
CONCLUSION
At any generation, mothers are likely to have daughters repeating their BF experience. Differently from the intergenerational effects of environmental factors responsible for the BF secular trend, this trait is transgenerationally transmitted and reversible, with temporal and clinical features of lactation failure. Accordingly, we speculate that epigenetic mechanisms might alter offspring's oxytocinergic receptor signalling.
WHAT IS KNOWN
Several cultural and socio-demographic factors are known to influence breastfeeding outcome. The generational effects of breastfeeding itself have not been investigated so far.
WHAT IS NEW
Maternal breastfeeding is the most important factor addressing daughters' breastfeeding outcome. This behavior is transmitted transgenerationally, with features suggesting epigenetic mechanisms.
Topics: Adult; Breast Feeding; Epigenomics; Female; Humans; Italy; Lactation; Pedigree; Prospective Studies
PubMed: 26264144
DOI: 10.1007/s00431-015-2605-6 -
Molecular Ecology Resources Nov 2022Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide...
Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obscure genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. Inbreeding is common in natural, domesticated, and experimental populations and genotyping of these populations often has more errors than in human data sets, so efficient methods for building pedigrees under these conditions are necessary. Here, we present a new method for parent-offspring inference in inbred pedigrees called specific parent-offspring relationship estimation (spore). spore is vastly superior to existing pedigree-inference methods at detecting parent-offspring relationships, in particular when inbreeding is high or in the presence of genotyping errors, or both. spore therefore fills an important void in the arsenal of pedigree inference tools.
Topics: Genome; Humans; Inbreeding; Models, Genetic; Pedigree
PubMed: 35770342
DOI: 10.1111/1755-0998.13680 -
Bioinformatics (Oxford, England) Mar 2018The collection, management and visualization of clinical pedigree (family history) data is a core activity in clinical genetics centres. However, clinical pedigree...
MOTIVATION
The collection, management and visualization of clinical pedigree (family history) data is a core activity in clinical genetics centres. However, clinical pedigree datasets can be difficult to manage, as they are time consuming to capture, and can be difficult to build, manipulate and visualize graphically. Several standalone graphical pedigree editors and drawing applications exist but there are no freely available lightweight graphical pedigree editors that can be easily configured and incorporated into web applications.
RESULTS
We developed 'pedigreejs', an interactive graphical pedigree editor written in JavaScript, which uses standard pedigree nomenclature. Pedigreejs provides an easily configurable, extensible and lightweight pedigree editor. It makes use of an open-source Javascript library to define a hierarchical layout and to produce images in scalable vector graphics (SVG) format that can be viewed and edited in web browsers.
AVAILABILITY AND IMPLEMENTATION
The software is freely available under GPL licence (https://ccge-boadicea.github.io/pedigreejs/).
CONTACT
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: Female; Humans; Internet; Male; Medical History Taking; Pedigree; Software; Web Browser
PubMed: 29095980
DOI: 10.1093/bioinformatics/btx705 -
BMC Medical Genomics Sep 2023To report novel pathogenic variants of X-linked genes in five Chinese families with early-onset high myopia (eoHM) by using whole-exome sequencing and analyzing the...
PURPOSE
To report novel pathogenic variants of X-linked genes in five Chinese families with early-onset high myopia (eoHM) by using whole-exome sequencing and analyzing the phenotypic features.
METHODS
5 probands with X-linked recessive related eoHM were collected in Ningxia Eye Hospital from January 2021 to June 2022. The probands and their family members received comprehensive ophthalmic examinations,and DNA was abstracted from patients and family members. Whole-exome sequencing was performed on probands to screen the causative variants, and all suspected pathogenic variants were determined by Sanger sequencing and co-segregation analysis was performed on available family members. The pathogenicity of novel variants was predicted using silico analysis and evaluated according to ACMG guidelines. RT-qPCR was used to detect differences in the relative mRNAs expression of candidate gene in mRNAs available with the proband and family members in the pedigree 2. The relationship between genetic variants and clinical features was analyzed.
RESULTS
All probands were male, and all pedigrees conformed to an X-linked recessive inheritance pattern. They were diagnosed with high myopia at their first visits between 4 and 7 years old. Spherical equivalent ranged between - 6.00D and - 11.00D.The five novel hemizygous variants were found in the probands, containing frameshift deletion variant c.797_801del (p.Val266Alafs*75) of OPN1LW gene in the pedigree 1, nonsense variant c.513G > A (p.Trp171Ter)of RP2 gene in the pedigree 2, missense variant c.98G > T (p.Cys33Phe) of GPR143 gene in the pedigree 3, frameshift deletion variant c.1876_1877del (p.Met626Valfs*22) of FRMD7 gene in the pedigree 4 and inframe deletion variant c.670_ 675del (p.Glu192_ Glu193del) of HMGB3 gene in the pedigree 5. All variants were classified as pathogenic or likely pathogenic by the interpretation principles of HGMD sequence variants and ACMG guidelines. In family 2, RT-qPCR showed that the mRNA expression of RP2 gene was lower in the proband than in other normal family members, indicating that such variant caused an effect on gene function at the mRNA expression level. Further clinical examination showed that pedigrees 1, 2, 3, and 4 were diagnosed as X-linked recessive hereditary eye disease with early-onset high myopia, including quiescent cone dysfunction, retinitis pigmentosa, ocular albinism, and idiopathic congenital nystagmus respectively. The pedigree 5 had eoHM in the right eye and ptosis in both eyes.
CONCLUSION
In this paper,we are the first to report five novel hemizygous variants in OPN1LW, RP2, GPR143, FRMD7, HMGB3 genes are associated with eoHM. Our study extends the genotypic spectrums for eoHM and better assists ophthalmologists in assessing, diagnosing, and conducting genetic screening for eoHM.
Topics: Child; Child, Preschool; Humans; Male; Cytoskeletal Proteins; East Asian People; Genes, X-Linked; Membrane Proteins; Mutation; Myopia; Age of Onset; Exome Sequencing; Pedigree
PubMed: 37749571
DOI: 10.1186/s12920-023-01665-x -
Current Protocols in Human Genetics Apr 2018In this article, we discuss strategies for selection of families and family members for genetic studies. We will evaluate strategies to sample large families with...
In this article, we discuss strategies for selection of families and family members for genetic studies. We will evaluate strategies to sample large families with multiply affected members, sibships, and nuclear families. In addition, we have added a section to discuss sub-sampling within pedigrees for large sequencing studies, particularly when genome-wide SNP chips are available on all members of a pedigree. The type of family sampled for a study will determine the statistical analyses and power of discovery of genetic findings. We will evaluate study designs that maximize power and allow for linkage and association analyses to identify genetic loci predisposing to phenotype. © 2018 by John Wiley & Sons, Inc.
Topics: Disease; Female; Genetic Linkage; Genetic Loci; Genetic Variation; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Male; Models, Genetic; Nuclear Family; Pedigree; Phenotype; Research Design
PubMed: 30040223
DOI: 10.1002/cphg.56 -
Molecular Ecology Resources Feb 2022In genomic-scale data sets, loci are closely packed within chromosomes and hence provide correlated information. Averaging across loci as if they were independent...
In genomic-scale data sets, loci are closely packed within chromosomes and hence provide correlated information. Averaging across loci as if they were independent creates pseudoreplication, which reduces the effective degrees of freedom (df') compared to the nominal degrees of freedom, df. This issue has been known for some time, but consequences have not been systematically quantified across the entire genome. Here, we measured pseudoreplication (quantified by the ratio df'/df) for a common metric of genetic differentiation (F ) and a common measure of linkage disequilibrium between pairs of loci (r ). Based on data simulated using models (SLiM and msprime) that allow efficient forward-in-time and coalescent simulations while precisely controlling population pedigrees, we estimated df' and df'/df by measuring the rate of decline in the variance of mean F and mean r as more loci were used. For both indices, df' increases with N and genome size, as expected. However, even for large N and large genomes, df' for mean r plateaus after a few thousand loci, and a variance components analysis indicates that the limiting factor is uncertainty associated with sampling individuals rather than genes. Pseudoreplication is less extreme for F , but df'/df ≤0.01 can occur in data sets using tens of thousands of loci. Commonly-used block-jackknife methods consistently overestimated var (F ), producing very conservative confidence intervals. Predicting df' based on our modelling results as a function of N , L, S, and genome size provides a robust way to quantify precision associated with genomic-scale data sets.
Topics: Genome Size; Genomics; Linkage Disequilibrium; Models, Genetic; Pedigree; Population Density
PubMed: 34351073
DOI: 10.1111/1755-0998.13482