scholarly journals Computational Inference, Validation, and Analysis of 5’UTR-Leader Sequences of Alleles of Immunoglobulin Heavy Chain Variable Genes

2021 ◽  
Vol 12 ◽  
Author(s):  
Yixun Huang ◽  
Linnea Thörnqvist ◽  
Mats Ohlin
Keyword(s):  
Heavy Chain ◽  
Population Data ◽  
Immunoglobulin Heavy Chain ◽  
Upstream Region ◽  
Data Sets ◽  
Generation Process ◽  
Data Set ◽  
Evolutionary Relatedness ◽  
Immunoglobulin Heavy Chain Genes ◽  
Variable Genes

Upstream and downstream sequences of immunoglobulin genes may affect the expression of such genes. However, these sequences are rarely studied or characterized in most studies of immunoglobulin repertoires. Inference from large, rearranged immunoglobulin transcriptome data sets offers an opportunity to define the upstream regions (5’-untranslated regions and leader sequences). We have now established a new data pre-processing procedure to eliminate artifacts caused by a 5’-RACE library generation process, reanalyzed a previously studied data set defining human immunoglobulin heavy chain genes, and identified novel upstream regions, as well as previously identified upstream regions that may have been identified in error. Upstream sequences were also identified for a set of previously uncharacterized germline gene alleles. Several novel upstream region variants were validated, for instance by their segregation to a single haplotype in heterozygotic subjects. SNPs representing several sequence variants were identified from population data. Finally, based on the outcomes of the analysis, we define a set of testable hypotheses with respect to the placement of particular alleles in complex IGHV locus haplotypes, and discuss the evolutionary relatedness of particular heavy chain variable genes based on sequences of their upstream regions.

scholarly journals Computational inference, validation, and analysis of 5'UTR-leader sequences of alleles of immunoglobulin heavy chain variable genes

2021 ◽  
Author(s):  
Yixun Huang ◽  
Linnea Thörnqvist ◽  
Mats Ohlin
Keyword(s):  
Heavy Chain ◽  
Population Data ◽  
Immunoglobulin Heavy Chain ◽  
Upstream Region ◽  
Data Sets ◽  
Generation Process ◽  
Data Set ◽  
Evolutionary Relatedness ◽  
Immunoglobulin Heavy Chain Genes ◽  
Variable Genes

Upstream and downstream sequences of immunoglobulin genes may affect the expression of such genes. However, these sequences are rarely studied or characterized in most studies of immunoglobulin repertoires. Inference from large, rearranged immunoglobulin transcriptome data sets offers an opportunity to define the upstream regions (5'-untranslated regions and leader sequences). We have now established a new data pre-processing procedure to eliminate artifacts caused by a 5'-RACE library generation process, reanalyzed a previously studied data set defining human immunoglobulin heavy chain genes, and identified novel upstream regions, as well as previously identified upstream regions that may have been identified in error. Upstream sequences were also identified for a set of previously uncharacterized germline gene alleles. Several novel upstream region variants were validated, for instance by their segregation to a single haplotype in heterozygotic subjects. SNPs representing several sequence variants were identified from population data. Finally, based on the outcomes of the analysis, we define a set of testable hypotheses with respect to the placement of particular alleles in complex IGHV locus haplotypes, and discuss the evolutionary relatedness of particular heavy chain variable genes based on sequences of their upstream regions.

scholarly journals Genotyping and Copy Number Analysis of Immunoglobulin Heavy Chain Variable Genes Using Long Reads

iScience ◽  
2020 ◽  
Vol 23 (9) ◽  
pp. 101508
Author(s):  
Michael Ford ◽  
Ehsan Haghshenas ◽  
Corey T. Watson ◽  
S. Cenk Sahinalp
Keyword(s):  
Heavy Chain ◽  
Copy Number ◽  
Immunoglobulin Heavy Chain ◽  
Copy Number Analysis ◽  
Long Reads ◽  
Variable Genes

Presence of N regions in the clonotypic DJ rearrangements of the immunoglobulin heavy-chain genes indicates an exquisitely short latency in t(4;11)-positive infant acute lymphoblastic leukemia

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2272-2274 ◽  
Author(s):  
Karin Fasching ◽  
Simon Panzer ◽  
Oskar A. Haas ◽  
Arndt Borkhardt ◽  
Rolf Marschalek ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Heavy Chain ◽  
Lymphoblastic Leukemia ◽  
Latency Period ◽  
Immunoglobulin Heavy Chain ◽  
In Utero ◽  
Cell Precursor ◽  
Developmentally Regulated ◽  
Igh Genes ◽  
Immunoglobulin Heavy Chain Genes

Childhood acute lymphoblastic leukemia (ALL) is frequently initiated in utero at a time of developmentally regulated insertion of N regions into the DJH rearrangements of immunoglobulin heavy-chain (IgH) genes. Here it is shown that N regions are present in the clonotypic DJH rearrangements in 11 of 12 infant ALLs with t(4;11). These data are compared with the 122 previously published DJH sequences and were found to have a pattern similar to that of ALL in children older than 3 years at diagnosis but were unlike that in children younger than 3 years who predominantly lack N regions. These findings, therefore, indicate that t(4;11)-positive infant ALL is initiated later in fetal development than most B-cell precursor ALL from children younger than 3 years and that they have a shorter latency period already in utero.

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