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Bioinformatics (Oxford, England) Jan 2023Genotyping by sequencing is a powerful tool for investigating genetic variation in plants, but many economically important plants are allopolyploids, where homoeologous...
MOTIVATION
Genotyping by sequencing is a powerful tool for investigating genetic variation in plants, but many economically important plants are allopolyploids, where homoeologous similarity obscures the subgenomic origin of reads and confounds allelic and homoeologous SNPs. Recent polyploid genotyping methods use allelic frequencies, rate of heterozygosity, parental cross or other information to resolve read assignment, but good subgenomic references offer the most direct information. The typical strategy aligns reads to the joint reference, performs diploid genotyping within each subgenome, and filters the results, but persistent read misassignment results in an excess of false heterozygous calls.
RESULTS
We introduce the Comprehensive Allopolyploid Genotyper (CAPG), which formulates an explicit likelihood to weight read alignments against both subgenomic references and genotype individual allopolyploids from whole-genome resequencing data. We demonstrate CAPG in allotetraploids, where it performs better than Genome Analysis Toolkit's HaplotypeCaller applied to reads aligned to the combined subgenomic references.
AVAILABILITY AND IMPLEMENTATION
Code and tutorials are available at https://github.com/Kkulkarni1/CAPG.git.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: Genotype; Genotyping Techniques; Sequence Analysis, DNA; Heterozygote; Alleles; Software; High-Throughput Nucleotide Sequencing
PubMed: 36367243
DOI: 10.1093/bioinformatics/btac729 -
Heredity Mar 2021Sexually antagonistic coevolution is predicted to lead to the divergence of male and female genotypes related to the effects of substances transferred by males at mating...
Sexually antagonistic coevolution is predicted to lead to the divergence of male and female genotypes related to the effects of substances transferred by males at mating on female physiology. The outcome of mating should thus depend on the specific combination of mating genotypes. Although mating has been shown to influence female immunity in diverse insect taxa, a male-female genotype-by-genotype effect on female immunity post mating remains largely unexplored. Here, we investigate the effects of mating on female decorated cricket baseline immunity and the potential for a male-genotype-by-female-genotype interaction affecting this response. Females from three distinct genotypic backgrounds were left unmated or singly mated in a fully reciprocal design to males from the same three genotypic backgrounds. Hemocytes and hemocyte microaggregations were quantified for female cellular immunity, and phenoloxidase, involved in melanization, and antibacterial activity for humoral immunity. In this system, female cellular immunity was more reactive to mating, and mating effects were genotype-dependent. Specifically, for hemocytes, a genotype-by-mating status interaction mediated the effect of mating per se, and a significant male-female genotype-by-genotype interaction determined hemocyte depletion post mating. Microaggregations were influenced by the female's genotype or that of her mate. Female humoral immune measures were unaffected, indicating that the propensity for post-mating effects on females is dependent on the component of baseline immunity. The genotype-by-genotype effect on hemocytes supports a role of sexual conflict in post-mating immune suppression, suggesting divergence of male genotypes with respect to modification of female post-mating immunity, and divergence of female genotypes in resistance to these effects.
Topics: Animals; Female; Genotype; Gryllidae; Immunity, Humoral; Male; Reproduction; Sexual Behavior, Animal
PubMed: 33219366
DOI: 10.1038/s41437-020-00384-8 -
Genome Biology Oct 2022Genotyping is a core application of high-throughput sequencing. We present KAGE, a genotyper for SNPs and short indels that is inspired by recent developments within...
Genotyping is a core application of high-throughput sequencing. We present KAGE, a genotyper for SNPs and short indels that is inspired by recent developments within graph-based genome representations and alignment-free methods. KAGE uses a pan-genome representation of the population to efficiently and accurately predict genotypes. Two novel ideas improve both the speed and accuracy: a Bayesian model incorporates genotypes from thousands of individuals to improve prediction accuracy, and a computationally efficient method leverages correlation between variants. We show that the accuracy of KAGE is at par with the best existing alignment-free genotypers, while being an order of magnitude faster.
Topics: Algorithms; Bayes Theorem; Genome, Human; Genotype; Genotyping Techniques; High-Throughput Nucleotide Sequencing; Humans; INDEL Mutation; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
PubMed: 36195962
DOI: 10.1186/s13059-022-02771-2 -
Journal of Nippon Medical School =... 2014Molecular genetic studies in the last 2 decades have revealed a link between several inherited cardiac arrhythmias and genes encoding for ion channels or other membrane... (Review)
Review
Molecular genetic studies in the last 2 decades have revealed a link between several inherited cardiac arrhythmias and genes encoding for ion channels or other membrane components. Two recent international expert consensus statements endorsed by 3 continental electrophysiology societies have updated the clinical and genetic diagnoses and management in patients with inherited arrhythmia syndromes, including congenital long QT syndrome (LQTS) and Brugada syndrome. Thirteen genotypes have been identified in 50% to 80% of clinically affected patients with congenital LQTS. Therefore, genotype-phenotype correlations have been investigated, especially, in the 3 major genotypes--LQT1, LQT2 and LQT3 syndromes--enabling genotype-specific management and therapy. On the other hand, less than half of patients with Brugada syndrome can be genotyped, and mainly for the sodium channel gene, SCN5A. However, recent advances in molecular genetic testing include genome-wide association studies using gene arrays and targeted, whole-exome and whole-genome next-generation sequencing techniques. In this article, I will review the clinical and genetic diagnoses in congenital LQTS and Brugada syndrome.
Topics: Arrhythmias, Cardiac; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Inheritance Patterns
PubMed: 25186574
DOI: 10.1272/jnms.81.203 -
Bioinformatics (Oxford, England) Aug 2020AlphaFamImpute is an imputation package for calling, phasing and imputing genome-wide genotypes in outbred full-sib families from single nucleotide polymorphism (SNP)...
SUMMARY
AlphaFamImpute is an imputation package for calling, phasing and imputing genome-wide genotypes in outbred full-sib families from single nucleotide polymorphism (SNP) array and genotype-by-sequencing (GBS) data. GBS data are increasingly being used to genotype individuals, especially when SNP arrays do not exist for a population of interest. Low-coverage GBS produces data with a large number of missing or incorrect naïve genotype calls, which can be improved by identifying shared haplotype segments between full-sib individuals. Here, we present AlphaFamImpute, an algorithm specifically designed to exploit the genetic structure of full-sib families. It performs imputation using a two-step approach. In the first step, it phases and imputes parental genotypes based on the segregation states of their offspring (i.e. which pair of parental haplotypes the offspring inherited). In the second step, it phases and imputes the offspring genotypes by detecting which haplotype segments the offspring inherited from their parents. With a series of simulations, we find that AlphaFamImpute obtains high-accuracy genotypes, even when the parents are not genotyped and individuals are sequenced at <1x coverage.
AVAILABILITY AND IMPLEMENTATION
AlphaFamImpute is available as a Python package from the AlphaGenes website http://www.AlphaGenes.roslin.ed.ac.uk/AlphaFamImpute.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: Genome; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Polymorphism, Single Nucleotide
PubMed: 32467963
DOI: 10.1093/bioinformatics/btaa499 -
Nucleic Acids Research May 2021Large scale catalogs of common genetic variants (including indels and structural variants) are being created using data from second and third generation whole-genome...
Large scale catalogs of common genetic variants (including indels and structural variants) are being created using data from second and third generation whole-genome sequencing technologies. However, the genotyping of these variants in newly sequenced samples is a nontrivial task that requires extensive computational resources. Furthermore, current approaches are mostly limited to only specific types of variants and are generally prone to various errors and ambiguities when genotyping complex events. We are proposing an ultra-efficient approach for genotyping any type of structural variation that is not limited by the shortcomings and complexities of current mapping-based approaches. Our method Nebula utilizes the changes in the count of k-mers to predict the genotype of structural variants. We have shown that not only Nebula is an order of magnitude faster than mapping based approaches for genotyping structural variants, but also has comparable accuracy to state-of-the-art approaches. Furthermore, Nebula is a generic framework not limited to any specific type of event. Nebula is publicly available at https://github.com/Parsoa/Nebula.
Topics: Computer Simulation; Databases, Genetic; Genomics; Genotype; Genotyping Techniques; High-Throughput Nucleotide Sequencing; INDEL Mutation; Polymorphism, Single Nucleotide; Software; Whole Genome Sequencing
PubMed: 33503255
DOI: 10.1093/nar/gkab025 -
Acta Medica Portuguesa 2011Infection with Hepatitis B is a public health problem worldwide. In Portugal, around 1% of the population is chronically infected. Some genotypes are only predominant in... (Review)
Review
INTRODUCTION
Infection with Hepatitis B is a public health problem worldwide. In Portugal, around 1% of the population is chronically infected. Some genotypes are only predominant in some geographical regions; however migration around the world can lead to the dissemination of the different genotypes. The heterogeneity of hepatitis B genotypes seems to be related to differences in clinical evolution of the infection and response to antiviral treatment.
AIM
The present study was designed to review the worldwide geographical distribution of Hepatitis B genotypes, and to analyze the possible relationships with the distribution of genotypes in Portugal.
METHODS
Studies of interest were identified by search on indexed journals. Search of Portuguese information was extended to conference proceedings in the areas of Virology and Hepatology.
RESULTS
In Asia genotypes B and C were prevalent; in the North of Africa the genotype D was prevalent, and in the East Coast genotype E was predominant. In the American continent the most predominant genotypes were A, D, F, G and H. In South America, Venezuela and Argentina showed a high prevalence of genotype F, in Brazil genotype A was prevalent. In Europe, including Portugal, genotypes A and D were predominant. In Portugal genotypes C, E and F were observed in Portuguese patients and in immigrant patients.
DISCUSSION
The pattern of global migration affects the pattern of genotype distribution, introducing genotypes in regions where the clinical outcome can differ from the population of origin. The genotypic distribution found in Portugal seems to be associated not just with being a European country, but also with immigration from Africa, Brazil, Eastern Europe, and Asian countries like China. The study of the hepatitis B genotypic distribution should be extended to all regions in Portugal, namely Lisbon where the immigration levels are higher, as well as to the autonomous regions of Portugal, the Azores and Madeira islands. The relationship between hepatitis B genotypes and pathogenicity remains largely unknown, however evidence suggests the clinical and public health relevance of these genotypes. Further research is needed, not only to know how genotypes affect the severity of liver disease, but also to understand if and how the response to treatments is influenced by hepatitis B virus genotype.
Topics: Genotype; Global Health; Hepatitis B virus; Humans; Portugal
PubMed: 22521016
DOI: No ID Found -
Journal of Genetics 2022gene, which encodes a-actinin-3 and actin-binding protein, has been found to be associated with strong athletic performance, especially among track and field athletes....
gene, which encodes a-actinin-3 and actin-binding protein, has been found to be associated with strong athletic performance, especially among track and field athletes. Therefore, in this study, our aim was to compare the allelic and genotype frequencies of the ACTN3 R577X variant among elite athletes specialized in different branches, and nonathletic controls in Turkey. In the present study, 316 subjects, including 168 athletes and 148 sedentary controls were genotyped for the R577X variant. Genotyping was conducted by polymerase chain reaction (PCR) method. Additionally, we evaluated the groups by dividing them as females and males. There were 48 females and 120 males in the athletes group, and 43 females and 105 males in the control group. Genetic associations were evaluated by chi-squire test or Fisher's exact test. There was a significant difference between the athletes and controls in terms of the R577X variant. RR and XX genotypes increased in the controls compared to the athletes, while RX genotype was higher in the athletes than the controls ( = 0.030). Then we evaluated the groups by separating them as females and males. Genotype distribution of the R577X differed between the male athletes and the male controls ( = 0.046). R577X RX genotype increased in the male athletes compared to the male control ( = 0.046). But R577X genotype and allele distribution was not significant between female athletes and female control group (>0.05). As far as we know, this study is the largest series examining the R577X variant in Turkish athletes. Our results support that the R577X variant has a heterozygous advantage in athletic performance in the Turkish population. However, epigenetic, gene-gene and gene-environment interactions affects athlete performance should not be forgotten.
Topics: Actinin; Athletes; Athletic Performance; Female; Genotype; Humans; Male; Turkey
PubMed: 35652203
DOI: No ID Found -
Saudi Medical Journal Mar 2022To establish the frequency of Dombrock (DO) blood group genotypes in Western Saudi Arabians and to compare the findings with other populations in the 1000 genomes...
OBJECTIVES
To establish the frequency of Dombrock (DO) blood group genotypes in Western Saudi Arabians and to compare the findings with other populations in the 1000 genomes database.
METHODS
This cross-sectional study was carried out between December 2018 and February 2019. A total of 440 blood samples in ethylenediaminetetraacetic acid tubes were collected from unrelated Saudi Arabian blood donors from Jeddah, Saudi Arabia. Deoxyribonucleic acid was extracted, followed by an allele-specific polymerase chain reaction for DO*01 and DO*02 alleles (, ). The allele and genotype frequencies were counted and compared to those in other populations using the Chi-squared test with Bonferroni adjustments.
RESULTS
The DO allele frequencies for blood donors from western Saudi Arabia were 0.432 for DO*01 and 0.568 for DO*02. The DO genotype frequencies were 0.182 for DO*01/01, 0.318 for DO*02/02, and 0.5 for DO*01/02. The DO genotype frequencies were similar to Europeans, Americans, and South Asians but significantly different from the genotype frequencies of Africans and East Asians reported in the 1000 genomes database.
CONCLUSION
Dombrock genotype frequencies in the Western Saudi Arabian population were different from Africans and East Asians but not from Europeans, Americans, and South Asians. This study contributes to a genotyped blood donor database and may advance transfusion safety for patients in western Saudi Arabia.
Topics: Blood Donors; Blood Group Antigens; Cross-Sectional Studies; Gene Frequency; Genotype; Humans; Saudi Arabia
PubMed: 35256491
DOI: 10.15537/smj.2022.43.3.20210680 -
Translational Psychiatry May 2021Pharmacogenetics aims to improve clinical care by studying the relationship between genetic variation and variable drug response. Large population-based datasets could...
Pharmacogenetics aims to improve clinical care by studying the relationship between genetic variation and variable drug response. Large population-based datasets could improve our current understanding of pharmacogenetics from selected study populations. We provide real-world pharmacogenetic frequencies of genotypes and (combined) phenotypes of a large Danish population-based case-cohort sample (iPSYCH2012; data of the Integrative Psychiatric Research consortium). The genotyped sample consists of 77,684 individuals, of which 51,464 individuals had diagnoses of severe mental disorders (SMD case-cohort) and 26,220 were individuals randomly selected from the Danish population (population cohort). Array-based genotype data imputed to 8.4 million genetic variants was searched for a selected pharmacogenetic panel of 42 clinically relevant variants and a CYP2D6 gene deletion and duplication. We identified 19 of 42 variants. Minor allele frequencies (MAFs) were consistent with previously reported MAFs, and did not differ between SMD cases and population cohorts. Almost all individuals carried at least one genetic variant (> 99.9%) and 87% carried three or more genetic variants. When genotypes were translated into phenotypes, also > 99.9% of individuals had at least one divergent phenotype (i.e. divergent from the common phenotypes considered normal, e.g. extensive metabolizer). The high number of identified individuals with at least one pharmacogenetic variant or divergent phenotype indicates the importance of pharmacogenetic panel-based genotyping. Combined CYP2C19-CYP2D6 phenotypes revealed that 72.7% of individuals had divergent phenotypes for one or both enzymes. As CYP2D6 and CYP2C19 have an important role in the metabolism of psychotropic drugs, this indicates the relevance of pharmacogenetic testing specifically in individuals using psychotropic drugs.
Topics: Denmark; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype
PubMed: 34006849
DOI: 10.1038/s41398-021-01417-4