scholarly journals Worldwide genetic variation of the IGHV and TRBV immune receptor gene families in humans

2017 ◽  
Author(s):  
Shishi Luo ◽  
Jane A. Yu ◽  
Heng Li ◽  
Yun S. Song
Keyword(s):  
Gene Duplication ◽  
Copy Number ◽  
Receptor Gene ◽  
Copy Number Variants ◽  
Gene Families ◽  
Functional Gene ◽  
Nucleotide Variation ◽  
Single Nucleotide Variation ◽  
Single Nucleotide ◽  
Variable Regions

AbstractThe immunoglobulin heavy variable (IGHV) and T cell beta variable (TRBV) loci are among the most complex and variable regions in the human genome. Generated through a process of gene duplication/deletion and diversification, these loci can vary extensively between individuals in copy number and contain genes that are highly similar, making their analysis technically challenging. Here, we present a comprehensive study of the functional gene segments in the IGHV and TRBV loci, quantifying their copy number and single nucleotide variation in a globally diverse sample of 109 (IGHV) and 286 (TRBV) humans from over a hundred populations. We find that the IGHV and TRBV gene families exhibit starkly different patterns of variation. In particular, with hundreds of copy number haplotypes (instances that have differences in the number of functional gene segments), the IGHV locus has undergone more frequent gene duplication/deletion compared to the TRBV locus, which has only a few copy number haplotypes. In contrast, the TRBV locus has a greater or at least equal propensity to mutate, as evidenced by greater single nucleotide variation, compared to the IGHV locus. Thus, despite common molecular and functional characteristics, the genes that comprise the IGHV and TRBV loci have evolved in strikingly different ways. As well as providing insight into the different evolutionary paths the IGHV and TRBV loci have taken, our results are also important to the adaptive immune repertoire sequencing community, where the lack of frequencies of common alleles and copy number variants is hampering existing analytical pipelines.

scholarly journals Worldwide genetic variation of the IGHV and TRBV immune receptor gene families in humans

2019 ◽  
Vol 2 (2) ◽  
pp. e201800221 ◽  
Author(s):  
Shishi Luo ◽  
Jane A Yu ◽  
Heng Li ◽  
Yun S Song
Keyword(s):  
Copy Number ◽  
Receptor Gene ◽  
Copy Number Variants ◽  
Gene Families ◽  
Single Nucleotide ◽  
Variable Regions ◽  
Repertoire Sequencing ◽  
Trbv Gene ◽  
Beta Variable ◽  
Evolutionary Paths

The immunoglobulin heavy variable (IGHV) and T cell beta variable (TRBV) loci are among the most complex and variable regions in the human genome. Generated through a process of gene duplication/deletion and diversification, these loci can vary extensively between individuals in copy number and contain genes that are highly similar, making their analysis technically challenging. Here, we present a comprehensive study of the functional gene segments in the IGHV and TRBV loci, quantifying their copy number and single-nucleotide variation in a globally diverse sample of 109 (IGHV) and 286 (TRBV) humans from over a 100 populations. We find that the IGHV and TRBV gene families exhibit starkly different patterns of variation. In addition to providing insight into the different evolutionary paths of the IGHV and TRBV loci, our results are also important to the adaptive immune repertoire sequencing community, where the lack of frequencies of common alleles and copy number variants is hampering existing analytical pipelines.

Sensitive analysis of single nucleotide variation by Cas13d orthologs, EsCas13d and RspCas13d

2021 ◽  
Author(s):  
Xin Qiao ◽  
Yanmin Gao ◽  
Jiaojiao Li ◽  
Zhaoguan Wang ◽  
Hongyan Qiao ◽  
...  
Keyword(s):  
Nucleotide Variation ◽  
Single Nucleotide Variation ◽  
Single Nucleotide ◽  
Sensitive Analysis

scholarly journals An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Leandro de Araújo Lima ◽  
Ana Cecília Feio-dos-Santos ◽  
Sintia Iole Belangero ◽  
Ary Gadelha ◽  
Rodrigo Affonseca Bressan ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Integrative Approach ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Hyperactivity Disorder ◽  
New Genes

Abstract Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two “in silico” protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.

Basic principles of genetic disease

ESC CardioMed ◽  
2018 ◽  
pp. 669-671
Author(s):  
Eric Schulze-Bahr
Keyword(s):  
Genetic Disease ◽  
Copy Number ◽  
Copy Number Variants ◽  
Single Nucleotide Variants ◽  
Individual Genome ◽  
Base Pairs ◽  
Single Nucleotide ◽  
Basic Principles ◽  
Bona Fide ◽  
Genomic Regions

The human genome consists of approximately 3 billion (3 × 109) base pairs of DNA (around 20,000 genes), organized as 23 chromosomes (diploid parental set), and a small mitochondrial genome (37 genes, including 13 proteins; 16,589 base pairs) of maternal origin. Most human genetic variation is natural, that is, common or rare (minor allele frequency >0.1%) and does not cause disease—apart from every true disease-causing (bona fide) mutation each individual genome harbours more than 3.5 million single nucleotide variants (including >10,000 non-synonymous changes causing amino acid substitutions) and 200–300 large structural or copy number variants (insertions/deletions, up to several thousands of base-pairs) that are non-disease-causing variations and scattered throughout coding and non-coding genomic regions.

scholarly journals Annotate-it: a Swiss-knife approach to annotation, analysis and interpretation of single nucleotide variation in human disease

10.1186/gm374 ◽  
2012 ◽  
Vol 4 (9) ◽  
pp. 73 ◽  
Author(s):  
Alejandro Sifrim ◽  
Jeroen KJ Van Houdt ◽  
Leon-Charles Tranchevent ◽  
Beata Nowakowska ◽  
Ryo Sakai ◽  
...  
Keyword(s):  
Human Disease ◽  
Nucleotide Variation ◽  
Single Nucleotide Variation ◽  
Single Nucleotide

Genetics of Schizophrenia and Bipolar Disorder

2017 ◽  
Author(s):  
Alexander Charney ◽  
Pamela Sklar
Keyword(s):  
Bipolar Disorder ◽  
Copy Number ◽  
Psychotic Disorders ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Common Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Number Variation

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.

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