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Journal of Applied Genetics May 2023Our objective was to establish a SNPs panel for pedigree reconstruction using microarrays of different densities and evaluate the genomic relationship coefficient of the...
Our objective was to establish a SNPs panel for pedigree reconstruction using microarrays of different densities and evaluate the genomic relationship coefficient of the inferred pedigree, in addition to analyzing the population structure based on genomic analyses in Gir cattle. For parentage analysis and genomic relationship, 16,205 genotyped Gir animals (14,458 females and 1747 males) and 1810 common markers to the four SNP microarrays were used. For population structure analyses, including linkage disequilibrium, effective population size, and runs of homozygosity (ROH), genotypes from 21,656 animals were imputed. Likelihood ratio (LR) approach was used to reconstruct the pedigree, deepening the pedigree and showing it is well established in terms of recent information. Coefficients for each relationship category of the inferred pedigree were adequate. Linkage disequilibrium showed rapid decay. We detected a decrease in the effective population size over the last 50 generations, with the average generation interval around 9.08 years. Higher ROH-based inbreeding coefficient in a class of short ROH segments, with moderate to high values, was also detected, suggesting bottlenecks in the Gir genome. Breeding strategies to minimize inbreeding and avoid massive use of few proven sires with high genetic value are suggested to maintain genetic variability in future generations. In addition, we recommend reducing the generation interval to maximize genetic progress and increase effective population size.
Topics: Animals; Female; Male; Cattle; Polymorphism, Single Nucleotide; Pedigree; Genotype; Homozygote; Inbreeding
PubMed: 36645582
DOI: 10.1007/s13353-023-00747-x -
Transfusion and Apheresis Science :... Dec 2022To analyze the molecular mechanism of rare B subgroup in the ABO blood group system and conduct pedigree investigations.
OBJECTIVE
To analyze the molecular mechanism of rare B subgroup in the ABO blood group system and conduct pedigree investigations.
METHODS
The blood group was detected by conventional serological method, and ABO gene of proband and her family was amplified and sequenced by polymerase chain reaction method.
RESULTS
The study showed that the proband was a B phenotype by conventional serological method. Her family's serological results were as follows, her father and eldest brother were B subgroup while her mother and second eldest brother were O group. The proband's ABO gene sequencing result was ABO*BW.27/ABO*O.01.02. Her father, mother and two elder brothers were ABO*BW.27/ABO*O.01.01, ABO*O.01.01/ABO*O.01.02, ABO*BW.27/ABO*O.01.02, ABO*O.01.01/ABO*O.01.02.
CONCLUSION
Conventional blood group serology combined with molecular diagnostic technology can accurately identify the B subgroup, and the pedigree investigation analysis showed that the proband's allelic mutation came from her father. She has gained a point mutation of c.905A>G on the basis of ABO*B.01.
Topics: Male; Female; Animals; Pedigree; Genotype; Alleles; Phenotype; ABO Blood-Group System; Molecular Biology
PubMed: 35842292
DOI: 10.1016/j.transci.2022.103509 -
Forensic Science International. Genetics Mar 2024The genetic component of forensic genetic genealogy (FGG) is an estimate of kinship, often conducted at genome scales between a great number of individuals. The promise...
The genetic component of forensic genetic genealogy (FGG) is an estimate of kinship, often conducted at genome scales between a great number of individuals. The promise of FGG is substantial: in concert with genealogical records and other nongenetic information, it can indirectly identify a person of interest. A downside of FGG is cost, as it is currently expensive and requires chemistries uncommon to forensic genetic laboratories (microarrays and high throughput sequencing). The more common benchtop sequencers can be coupled with a targeted PCR assay to conduct FGG, though such approaches have limited resolution for kinship. This study evaluates low-pass sequencing, an alternative strategy that is accessible to benchtop sequencers and can produce resolutions comparable to high-pass sequencing. Samples from a three-generation pedigree were augmented to include up to 7th degree relatives (using whole genome pedigree simulations) and the ability to recover the true kinship coefficient was assessed using algorithms qualitatively similar to those found in GEDmatch. We show that up to 7th degree relatives can be reliably inferred from 1 × whole genome sequencing obtainable from desktop sequencers.
Topics: Humans; Algorithms; High-Throughput Nucleotide Sequencing; Pedigree; Polymorphism, Single Nucleotide; Genotype; DNA Fingerprinting
PubMed: 38171224
DOI: 10.1016/j.fsigen.2023.103005 -
Heredity Jan 2022The two alleles an individual carries at a locus are identical by descent (ibd) if they have descended from a single ancestral allele in a reference population, and the...
The two alleles an individual carries at a locus are identical by descent (ibd) if they have descended from a single ancestral allele in a reference population, and the probability of such identity is the inbreeding coefficient of the individual. Inbreeding coefficients can be predicted from pedigrees with founders constituting the reference population, but estimation from genetic data is not possible without data from the reference population. Most inbreeding estimators that make explicit use of sample allele frequencies as estimates of allele probabilities in the reference population are confounded by average kinships with other individuals. This means that the ranking of those estimates depends on the scope of the study sample and we show the variation in rankings for common estimators applied to different subdivisions of 1000 Genomes data. Allele-sharing estimators of within-population inbreeding relative to average kinship in a study sample, however, do have invariant rankings across all studies including those individuals. They are unbiased with a large number of SNPs. We discuss how allele sharing estimates are the relevant quantities for a range of empirical applications.
Topics: Alleles; Gene Frequency; Humans; Inbreeding; Models, Genetic; Pedigree; Polymorphism, Single Nucleotide
PubMed: 34824382
DOI: 10.1038/s41437-021-00471-4 -
BMC Bioinformatics Jun 2022The ubiquity of pedigrees in many scientific areas calls for versatile and user-friendly software. Previously published online pedigree tools have limited support for...
BACKGROUND
The ubiquity of pedigrees in many scientific areas calls for versatile and user-friendly software. Previously published online pedigree tools have limited support for complex pedigrees and do not provide analysis of relatedness between pedigree members.
RESULTS
We introduce QuickPed, a web application for interactive pedigree creation and analysis. It supports complex inbreeding and comes with a rich built-in library of common and interesting pedigrees. The program calculates all standard coefficients of relatedness, including inbreeding, kinship and identity coefficients, and offers specialised plots for visualising relatedness. It also implements a novel algorithm for describing pairwise relationships in words.
CONCLUSION
QuickPed is a user-friendly pedigree tool aimed at researchers, case workers and teachers. It contains a number of features not found in other similar tools, and represents a significant addition to the body of pedigree software by making advanced relatedness analyses available for non-bioinformaticians.
Topics: Algorithms; Humans; Inbreeding; Pedigree; Software
PubMed: 35672681
DOI: 10.1186/s12859-022-04759-y -
Proceedings of the National Academy of... May 2024Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However,...
Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the best method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. We simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structures (from the 1,000 Genomes project). We compare the ability of various inbreeding coefficients ([Formula: see text]) to quantify the strength of inbreeding depression: allele-sharing, two versions of the correlation of uniting gametes which differ in the weight they attribute to each locus and two identical-by-descent segments-based estimators. We also compare two models: the standard linear model and a linear mixed model (LMM) including a genetic relatedness matrix (GRM) as random effect to account for the nonindependence of observations. We find LMMs give better results in scenarios with population or family structure. Within the LMM, we compare three different GRMs and show that in homogeneous populations, there is little difference among the different [Formula: see text] and GRM for inbreeding depression quantification. However, as soon as a strong population or family structure is present, the strength of inbreeding depression can be most efficiently estimated only if i) the phenotypes are regressed on [Formula: see text] based on a weighted version of the correlation of uniting gametes, giving more weight to common alleles and ii) with the GRM obtained from an allele-sharing relatedness estimator.
Topics: Humans; Inbreeding Depression; Models, Genetic; Pedigree; Genetics, Population; Inbreeding; Alleles
PubMed: 38687793
DOI: 10.1073/pnas.2315780121 -
European Journal of Medical Genetics Dec 2023Biallelic pathogenic variants in CLDN10 cause the very rare and distinct multiplex epithelium dysfunction manifested by hypohidrosis and electrolyte imbalance (HELIX)... (Review)
Review
Biallelic pathogenic variants in CLDN10 cause the very rare and distinct multiplex epithelium dysfunction manifested by hypohidrosis and electrolyte imbalance (HELIX) syndrome. HELIX patients often present with heat intolerance and reduced tear secretion. Here, we report on eight new patients (four families) who presented soon after birth with fine scales in the palms and soles and hypohidrosis that was associated with high body temperature. Exome sequencing identified a novel homozygous pathogenic variant in CLDN10 in one family (NM_006984:exon1:c.138G>A:p.W46*) and a previously reported pathogenic founder variant in the other three (NM_006984:exon5:c.653del:P218Lfs*21). The detailed clinical reports of these patients and a review of previously reported patients further delineate the phenotype of this extremely rare disorder.
Topics: Humans; Hypohidrosis; Syndrome; Phenotype; Pedigree
PubMed: 37984702
DOI: 10.1016/j.ejmg.2023.104886 -
The Medical Clinics of North America Nov 2019The collection of family history has always been a tool for genetic evaluation, but it remains an essential tool even in the age of genomic medicine. Patients may have a... (Review)
Review
The collection of family history has always been a tool for genetic evaluation, but it remains an essential tool even in the age of genomic medicine. Patients may have a risk for a disease based on family history regardless of the results of genetic and genomic tests. How this information is collected is less important than that relevant information is collected in the first place. There are many tools for collecting medical and family history information both by hand and electronically. Genetic and genomic testing should always be interpreted in the context of the personal and family history.
Topics: Genetic Testing; Humans; Medical History Taking; Pedigree; Precision Medicine; Risk Assessment
PubMed: 31582006
DOI: 10.1016/j.mcna.2019.06.002 -
American Journal of Human Genetics Jan 2021The proportion of samples with one or more close relatives in a genetic dataset increases rapidly with sample size, necessitating relatedness modeling and enabling...
The proportion of samples with one or more close relatives in a genetic dataset increases rapidly with sample size, necessitating relatedness modeling and enabling pedigree-based analyses. Despite this, relatives are generally unreported and current inference methods typically detect only the degree of relatedness of sample pairs and not pedigree relationships. We developed CREST, an accurate and fast method that identifies the pedigree relationships of close relatives. CREST utilizes identity by descent (IBD) segments shared between a pair of samples and their mutual relatives, leveraging the fact that sharing rates among these individuals differ across pedigree configurations. Furthermore, CREST exploits the profound differences in sex-specific genetic maps to classify pairs as maternally or paternally related-e.g., paternal half-siblings-using the locations of autosomal IBD segments shared between the pair. In simulated data, CREST correctly classifies 91.5%-100% of grandparent-grandchild (GP) pairs, 80.0%-97.5% of avuncular (AV) pairs, and 75.5%-98.5% of half-siblings (HS) pairs compared to PADRE's rates of 38.5%-76.0% of GP, 60.5%-92.0% of AV, 73.0%-95.0% of HS pairs. Turning to the real 20,032 sample Generation Scotland (GS) dataset, CREST identified seven pedigrees with incorrect relationship types or maternal/paternal parent sexes, five of which we confirmed as mistakes, and two with uncertain relationships. After correcting these, CREST correctly determines relationship types for 93.5% of GP, 97.7% of AV, and 92.2% of HS pairs that have sufficient mutual relative data; the parent sex in 100% of HS and 99.6% of GP pairs; and it completes this analysis in 2.8 h including IBD detection in eight threads.
Topics: Female; Genetic Linkage; Genome, Human; Genotype; Humans; Male; Models, Genetic; Pedigree; Scotland
PubMed: 33385324
DOI: 10.1016/j.ajhg.2020.12.004 -
Human Mutation May 2022Clinical genetic sequencing tests often identify variants of uncertain significance. One source of data that can help classify the pathogenicity of variants is familial...
Clinical genetic sequencing tests often identify variants of uncertain significance. One source of data that can help classify the pathogenicity of variants is familial cosegregation analysis. Identifying and genotyping relatives for cosegregation analysis can be time consuming and costly. We propose an algorithm that describes a single measure of expected variant information gain from genotyping a single additional relative in a family. Then we explore the performance of this algorithm by comparing actual recruitment strategies used in 35 families who had pursued cosegregation analysis with synthetic pedigrees of possible testing outcomes if the families had pursued an optimized testing strategy instead. For each actual and synthetic pedigree, we calculated the likelihood ratio of pathogenicity as each successive test was added to the pedigree. We analyzed the differences in cosegregation likelihood ratio over time resulting from actual versus optimized testing approaches. Employing the testing strategy indicated by the algorithm would have led to maximal information more rapidly in 30 of the 35 pedigrees (86%). Many clinical and research laboratories are involved in targeted cosegregation analysis. The algorithm we present can facilitate a data driven approach to optimal relative recruitment and genotyping for cosegregation analysis and more efficient variant classification.
Topics: Algorithms; Genetic Testing; Genetic Variation; Humans; Pedigree
PubMed: 35225377
DOI: 10.1002/humu.24363