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The Journal of Pediatrics Dec 2023
Topics: Humans; Nails, Malformed; Pedigree
PubMed: 37562741
DOI: 10.1016/j.jpeds.2023.113664 -
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 -
Molecular Ecology Oct 2018The concept of kinship permeates many domains of fundamental and applied biology ranging from social evolution to conservation science to quantitative and human...
The concept of kinship permeates many domains of fundamental and applied biology ranging from social evolution to conservation science to quantitative and human genetics. Until recently, pedigrees were the gold standard to infer kinship, but the advent of next-generation sequencing and the availability of dense genetic markers in many species make it a good time to (re)evaluate the usefulness of genetic markers in this context. Using three published data sets where both pedigrees and markers are available, we evaluate two common and a new genetic estimator of kinship. We show discrepancies between pedigree values and marker estimates of kinship and explore via simulations the possible reasons for these. We find these discrepancies are attributable to two main sources: pedigree errors and heterogeneity in the origin of founders. We also show that our new marker-based kinship estimator has very good statistical properties and behaviour and is particularly well suited for situations where the source population is of small size, as will often be the case in conservation biology, and where high levels of kinship are expected, as is typical in social evolution studies.
Topics: Genetic Markers; Genetics, Population; Humans; Models, Genetic; Pedigree
PubMed: 30107060
DOI: 10.1111/mec.14833 -
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 -
Neurological Sciences : Official... Jun 2023Neuronal intranuclear inclusion disease (NIID) is a rare but probably underdiagnosed neurodegenerative disorder due to pathogenic GGC expansions in the NOTCH2NLC gene.... (Review)
Review
Neuronal intranuclear inclusion disease (NIID) is a rare but probably underdiagnosed neurodegenerative disorder due to pathogenic GGC expansions in the NOTCH2NLC gene. In this review, we summarize recent developments in the inheritance features, pathogenesis, and histopathologic and radiologic features of NIID that subvert the previous perceptions of NIID. GGC repeat sizes determine the age of onset and clinical phenotypes of NIID patients. Anticipation may be absent in NIID but paternal bias is observed in NIID pedigrees. Eosinophilic intranuclear inclusions in skin tissues once considered pathological hallmarks of NIID can also present in other GGC repeat diseases. Diffusion-weighted imaging (DWI) hyperintensity along the corticomedullary junction once considered the imaging hallmark of NIID can frequently be absent in muscle weakness and parkinsonism phenotype of NIID. Besides, DWI abnormalities can appear years after the onset of predominant symptoms and may even disappear completely with disease progression. Moreover, continuous reports of NOTCH2NLC GGC expansions in patients with other neurodegenerative diseases lead to the proposal of a new concept of NOTCH2NLC-related GGC repeat expansion disorders (NRED). However, by reviewing the previous literature, we point out the limitations of these studies and provide evidence that these patients are actually suffering from neurodegenerative phenotypes of NIID.
Topics: Humans; Intranuclear Inclusion Bodies; Neurodegenerative Diseases; Diffusion Magnetic Resonance Imaging; Pedigree
PubMed: 36795299
DOI: 10.1007/s10072-023-06677-0 -
Twin Research and Human Genetics : the... Aug 2018Like families, professors transmit bits of wisdom to their students, not just by what they say but what they do. Colleagues share methods and data, but more importantly,... (Review)
Review
Like families, professors transmit bits of wisdom to their students, not just by what they say but what they do. Colleagues share methods and data, but more importantly, ideas and visions. Irving I. Gottesman was unique in this respect, both brilliant in his field and wise when it came to teaching, guiding, and supporting. His academic pedigree extends across many generations and will for generations to come.
Topics: Biomedical Research; Female; Human Genetics; Humans; Male; Pedigree; Twins
PubMed: 30027870
DOI: 10.1017/thg.2018.37 -
Methods in Molecular Biology (Clifton,... 2017Structural equation modeling (SEM) is a multivariate statistical framework that is used to model complex relationships between directly observed and indirectly observed...
Structural equation modeling (SEM) is a multivariate statistical framework that is used to model complex relationships between directly observed and indirectly observed (latent) variables. SEM is a general framework that involves simultaneously solving systems of linear equations and encompasses other techniques such as regression, factor analysis, path analysis, and latent growth curve modeling. Recently, SEM has gained popularity in the analysis of complex genetic traits because it can be used to better analyze the relationships between correlated variables (traits), to model genes as latent variables as a function of multiple observed genetic variants, and to assess the association between multiple genetic variants and multiple correlated phenotypes of interest. Though the general SEM framework only allows for the analysis of independent observations, recent work has extended SEM for the analysis of data on general pedigrees. Here, we review the theory of SEM for both unrelated and family data, describe the available software for SEM, and provide examples of SEM analysis.
Topics: Algorithms; Genetic Variation; Humans; Models, Genetic; Models, Statistical; Multivariate Analysis; Pedigree; Phenotype; Software
PubMed: 28980265
DOI: 10.1007/978-1-4939-7274-6_28 -
American Journal of Medical Genetics.... May 2023Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven... (Review)
Review
Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher™). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life-limiting congenital anomalies.
Topics: Pregnancy; Female; Humans; Child; Phenotype; Ciliopathies; Pedigree; Adaptor Proteins, Signal Transducing
PubMed: 36826837
DOI: 10.1002/ajmg.a.63150 -
Semergen Apr 2022A genogram and a genealogical tree are graphic representations of families that share similarities but have different functionality and meanings. While the first basic...
A genogram and a genealogical tree are graphic representations of families that share similarities but have different functionality and meanings. While the first basic objective is to represent the family structure and the relationships between its members, the second seeks to identify the inheritance pattern and inheritable traits, although its use and applications go much further. Graphic representation is normalized with similar symbols, although some of them have different meanings. Both are used by family doctors, and they must have the necessary skills for their effective management. This work aims to improve these skills by defining the main differences between the two tools, establishing the basic elements for the construction and interpretation of a genealogical tree, and pointing out its clinical utility and its most frequent uses.
Topics: Family Relations; Humans; Pedigree; Phenotype
PubMed: 35172955
DOI: 10.1016/j.semerg.2021.10.005 -
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