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Nature Communications Apr 2023Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set...
Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in FOXI3. Biochemical experiments on transcriptional activity and subcellular localization of the likely pathogenic FOXI3 variants, and knock-in mouse studies strongly support the involvement of FOXI3 in CFM. Our findings indicate autosomal dominant inheritance with reduced penetrance, and/or autosomal recessive inheritance. The phenotypic expression of the FOXI3 variants is variable. The penetrance of the likely pathogenic variants in the seemingly dominant form is reduced, since a considerable number of such variants in affected individuals were inherited from non-affected parents. Here we provide suggestive evidence that common variation in the FOXI3 allele in trans with the pathogenic variant could modify the phenotypic severity and accounts for the incomplete penetrance.
Topics: Animals; Mice; Goldenhar Syndrome; Facial Asymmetry; Pedigree; Forkhead Transcription Factors
PubMed: 37041148
DOI: 10.1038/s41467-023-37703-6 -
Taiwanese Journal of Obstetrics &... Mar 2022To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic...
OBJECTIVES
To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic diagnosis by chorionic villus for these pedigrees.
MATERIALS AND METHODS
Gene analyses were performed for 244 pedigrees. There are 130 pedigrees, chorionic villus sampling was performed on the pregnant women to conduct the prenatal diagnosis.
RESULTS
Among 244 patients, 168 (68.9%) cases were combined methylmalonic aciduria and homocystinuria, 76 (31.1%) cases were isolated methylmalonic aciduria. All the patients were diagnosed with MMA by their clinical manifestation, elevated blood propionylcarnitine, propionylcarnitine to acetylcarnitine ratio, and/or urine/blood methylmalonic acid with or without homocysteine. MMACHC, MMUT, SUCLG1 and LMBRD1 gene variants were found in 236 (96.7%) pedigrees included 6 probands with only one heterozygous variant out of 244 cases. For the 130 pedigrees who received a prenatal diagnosis, 22 fetuses were normal, 69 foetuses were carriers of heterozygous variants, and the remaining 39 foetuses harboured compound heterozygous variants or homozygous variants. The follow-up results were consistent with the prenatal diagnosis.
CONCLUSION
The present study indicates genetic heterogeneity in MMA patients. Genetic analysis is a convenient method for prenatal diagnosis that will aid in avoiding the delivery of MMA patients.
Topics: Amino Acid Metabolism, Inborn Errors; China; Female; Genotype; Humans; Nucleocytoplasmic Transport Proteins; Oxidoreductases; Pedigree; Pregnancy; Prenatal Diagnosis
PubMed: 35361390
DOI: 10.1016/j.tjog.2022.02.017 -
European Journal of Human Genetics :... Jan 2022
Topics: Deafness; Humans; Pedigree
PubMed: 34819629
DOI: 10.1038/s41431-021-01006-5 -
Ugeskrift For Laeger Jul 2021This is a case report of a patient, who was diagnosed with epilepsy (atypical infantile convulsions) at the age of one year and unspecific myopathy at the age of three...
This is a case report of a patient, who was diagnosed with epilepsy (atypical infantile convulsions) at the age of one year and unspecific myopathy at the age of three years. At the age of 25 years, the patient was referred to a neuromuscular clinic due to myopathy, but the diagnose was changed to atypical infantile convulsions with seizures in adulthood and paroxysmal choreoathetosis due to a pathogenic variant c.970G>A, p. (Gly324Arg) in the PRRT2 gene.
Topics: Adult; Dyskinesias; Epilepsy, Benign Neonatal; Humans; Infant; Membrane Proteins; Mutation; Nerve Tissue Proteins; Pedigree
PubMed: 34356019
DOI: No ID Found -
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 -
Journal of Dairy Science Feb 2022Single-step genomic BLUP (ssGBLUP) is a method for genomic prediction that integrates matrices of pedigree (A) and genomic (G) relationships into a single unified... (Review)
Review
Single-step genomic BLUP (ssGBLUP) is a method for genomic prediction that integrates matrices of pedigree (A) and genomic (G) relationships into a single unified additive relationship matrix whose inverse is incorporated into a set of mixed model equations (MME) to compute genomic predictions. Pedigree information in dairy cattle is often incomplete. Missing pedigree potentially causes biases and inflation in genomic estimated breeding values (GEBV) obtained with ssGBLUP. Three major issues are associated with missing pedigree in ssGBLUP, namely biased predictions by selection, missing inbreeding in pedigree relationships, and incompatibility between G and A in level and scale. These issues can be solved using a proper model for unknown-parent groups (UPG). The theory behind the use of UPG is well established for pedigree BLUP, but not for ssGBLUP. This study reviews the development of the UPG model in pedigree BLUP, the properties of UPG models in ssGBLUP, and the effect of UPG on genetic trends and genomic predictions. Similarities and differences between UPG and metafounder (MF) models, a generalized UPG model, are also reviewed. A UPG model (QP) derived using a transformation of the MME has a good convergence behavior. However, with insufficient data, the QP model may yield biased genetic trends and may underestimate UPG. The QP model can be altered by removing the genomic relationships linking GEBV and UPG effects from MME. This altered QP model exhibits less bias in genetic trends and less inflation in genomic predictions than the QP model, especially with large data sets. Recently, a new model, which encapsulates the UPG equations into the pedigree relationships for genotyped animals, was proposed in simulated purebred populations. The MF model is a comprehensive solution to the missing pedigree issue. This model can be a choice for multibreed or crossbred evaluations if the data set allows the estimation of a reasonable relationship matrix for MF. Missing pedigree influences genetic trends, but its effect on the predictability of genetic merit for genotyped animals should be negligible when many proven bulls are genotyped. The SNP effects can be back-solved using GEBV from older genotyped animals, and these predicted SNP effects can be used to calculate GEBV for young-genotyped animals with missing parents.
Topics: Animals; Cattle; Genome; Genomics; Genotype; Male; Models, Genetic; Pedigree; Phenotype
PubMed: 34799109
DOI: 10.3168/jds.2021-20293 -
Atherosclerosis May 2020Atherosclerosis and its major clinical manifestations – myocardial infarction, ischemic stroke and peripheral artery disease – remain a leading cause of death...
Atherosclerosis and its major clinical manifestations – myocardial infarction, ischemic stroke and peripheral artery disease – remain a leading cause of death worldwide. The onset of atherosclerosis is driven by the accumulation and expansion of macrophages in the artery wall in response to lipid deposition. Subsequently, the macrophage’s failure to resolve the inflammation and to exit the plaque are key processes in the progression of atherosclerosis. Understanding the underlying causes and pathological mechanisms of this chronic, low grade inflammation that sustains plaque progression has been a major focus of the field in the last decade. In this issue of , Bruikman et al identify a rare variant in the gene encoding the neuroimmune guidance molecule netrin-1 (), in a family with premature atherosclerosis, that alters netrin-1 functions and promotes proatherogenic immune responses.
Topics: Atherosclerosis; Humans; Mutation; Netrin-1; Pedigree
PubMed: 32317107
DOI: 10.1016/j.atherosclerosis.2020.04.003 -
Bioinformatics (Oxford, England) Jul 2023The resemble between relatives computed from pedigree and genomic data is an important resource for geneticists and ecologists, who are interested in understanding how...
MOTIVATION
The resemble between relatives computed from pedigree and genomic data is an important resource for geneticists and ecologists, who are interested in understanding how genes influence phenotypic variation, fitness adaptation, and population dynamics.
RESULTS
The AGHmatrix software is an R package focused on the construction of pedigree (A matrix) and/or molecular markers (G matrix), with the possibility of building a combined matrix of pedigree corrected by molecular markers (H matrix). Designed to estimate the relationships for any ploidy level, the software also includes auxiliary functions related to filtering molecular markers, and checks pedigree errors in large data sets. After computing the relationship matrices, results from the AGHmatrix can be used in different contexts, including on prediction of (genomic) estimated breeding values and genome-wide association studies.
AVAILABILITY AND IMPLEMENTATION
AGHmatrix v2.1.0 is available under GPL-3 license in CRAN at https://cran.r-project.org/web/packages/AGHmatrix/index.html and also in GitHub at https://github.com/rramadeu/AGHmatrix. It has a comprehensive tutorial, and it follows with real data examples.
Topics: Genome-Wide Association Study; Software; Genomics; Ploidies; Pedigree
PubMed: 37471595
DOI: 10.1093/bioinformatics/btad445 -
Genetics, Selection, Evolution : GSE Oct 2022Red dairy cattle breeds have an important role in the European dairy sector because of their functional characteristics and good health. Extensive pedigree information...
BACKGROUND
Red dairy cattle breeds have an important role in the European dairy sector because of their functional characteristics and good health. Extensive pedigree information is available for these breeds and provides a unique opportunity to examine their population structure, such as effective population size, depth of the pedigree, and effective number of founders and ancestors, and inbreeding levels. Animals with the highest genetic contributions were identified. Pedigree data included 9,073,403 animals that were born between 1900 and 2019 from Denmark, Finland, Germany, Latvia, Lithuania, the Netherlands, Norway, Poland, and Sweden, and covered 32 breeds. The numerically largest breeds were Red Dairy Cattle and Meuse-Rhine-Yssel.
RESULTS
The deepest average complete generation equivalent (9.39) was found for Red Dairy Cattle in 2017. Mean pedigree completeness ranged from 0.6 for Finncattle to 7.51 for Red Dairy Cattle. An effective population size of 166 animals was estimated for the total pedigree and ranged from 35 (Rotes Höhenvieh) to 226 (Red Dairy Cattle). Average generation intervals were between 5 and 7 years. The mean inbreeding coefficient for animals born between 1960 and 2018 was 1.5%, with the highest inbreeding coefficients observed for Traditional Angler (4.2%) and Rotes Höhenvieh (4.1%). The most influential animal was a Dutch Meuse-Rhine-Yssel bull born in 1960. The mean inbreeding level for animals born between 2016 and 2018 was 2% and highest for the Meuse-Rhine-Yssel (4.64%) and Rotes Hohenvieh breeds (3.80%).
CONCLUSIONS
We provide the first detailed analysis of the genetic diversity and inbreeding levels of the European red dairy cattle breeds. Rotes Höhenvieh and Traditional Angler have high inbreeding levels and are either close to or below the minimal recommended effective population size, thus it is necessary to implement tools to monitor the selection process in order to control inbreeding in these breeds. Red Dairy Cattle, Vorderwälder, Swedish Polled and Hinterwälder hold more genetic diversity. Regarding the Meuse-Rhine-Yssel breed, given its decreased population size, increased inbreeding and low effective population size, we recommend implementation of a breeding program to prevent further loss in its genetic diversity.
Topics: Cattle; Animals; Male; Inbreeding; Pedigree; Genetic Variation; Population Density; Records
PubMed: 36274137
DOI: 10.1186/s12711-022-00761-3 -
CBE Life Sciences Education Mar 2022Pedigree problems are typical genetics tasks in schools. They are well suited to help students learn scientific reasoning, representing realistic genetic problems....
Pedigree problems are typical genetics tasks in schools. They are well suited to help students learn scientific reasoning, representing realistic genetic problems. However, pedigree problems also pose complex requirements, especially for secondary students. They require a suitable solution strategy and technical knowledge. In this study, we examined the approaches used by = 89 secondary school students when solving two different pedigree problems. In our qualitative analysis of student responses, we examined how two groups of secondary students with varying degrees of experience in genetics constructed arguments to support their decisions. To do so, we categorized = 516 propositions from students' responses using theory- and data-driven codes. Comparison between groups revealed that "advanced genetics" students ( = 44) formulated more arguments, referred more frequently to specific family constellations, and considered superficial pedigree features less often. Conversely, "beginning genetics" students did not use a conclusive approach of step-by-step falsification but argued for the mode of inheritance they believed was correct. Advanced genetics students, in contrast to beginners, to some extent used a falsification strategy. Finally, we demonstrate which family members students used in their decisions and discuss a variety of typical but unreliable arguments.
Topics: Humans; Learning; Pedigree; Problem Solving; Schools; Students
PubMed: 35084933
DOI: 10.1187/cbe.21-01-0009