Record Details

Segmental duplication as one of the driving forces underlying the diversity of the human immunoglobulin heavy chain variable gene region

IR@CSIR-NEERI

View Archive Info
 
 
Field Value
 
Title Segmental duplication as one of the driving forces underlying the diversity of the human immunoglobulin heavy chain variable gene region
 
Creator Pramanik , Sreemanta
Cui, Xiangfeng
Wang, Hui-Yun
Chimge, Nyam-Osor
Hu, Guohong
Shen, Li
Gao, Richeng
Li, Honghua
 
Subject Environmental Health
 
Description Background: Segmental duplication and deletion were implicated for a region containing the human
immunoglobulin heavy chain variable (IGHV) gene segments, 1.9III/hv3005 (possible allelic variants of IGHV3-30) and
hv3019b9 (a possible allelic variant of IGHV3-33). However, very little is known about the ranges of the duplication
and the polymorphic region. This is mainly because of the difficulty associated with distinguishing between allelic
and paralogous sequences in the IGHV region containing extensive repetitive sequences. Inability to separate the
two parental haploid genomes in the subjects is another serious barrier. To address these issues, unique DNA
sequence tags evenly distributed within and flanking the duplicated region implicated by the previous studies were
selected. The selected tags in single sperm from six unrelated healthy donors were amplified by multiplex PCR
followed by microarray detection. In this way, individual haplotypes of different parental origins in the sperm donors
could be analyzed separately and precisely. The identified polymorphic region was further analyzed at the nucleotide
sequence level using sequences from the three human genomic sequence assemblies in the database.
Results: A large polymorphic region was identified using the selected sequence tags. Four of the 12 haplotypes were
shown to contain consecutively undetectable tags spanning in a variable range. Detailed analysis of sequences from
the genomic sequence assemblies revealed two large duplicate sequence blocks of 24,696 bp and 24,387 bp,
respectively, and an incomplete copy of 961 bp in this region. It contains up to 13 IGHV gene segments depending on
haplotypes. A polymorphic region was found to be located within the duplicated blocks. The variants of this
polymorphism unusually diverged at the nucleotide sequence level and in IGHV gene segment number, composition
and organization, indicating a limited selection pressure in general. However, the divergence level within the gene
segments is significantly different from that in the intergenic regions indicating that these regions may have been
subject to different selection pressures and that the IGHV gene segments in this region are functionally important.
Conclusions: Non-reciprocal genetic rearrangements associated with large duplicate sequence blocks could
substantially contribute to the IGHV region diversity. Since the resulting polymorphisms may affect the number,
composition and organization of the gene segments in this region, it may have significant impact on the function
of the IGHV gene segment repertoire, antibody diversity, and therefore, the immune system. Because one of the
gene segments, 3-30 (1.9III), is associated with autoimmune diseases, it could be of diagnostic significance to learn
about the variants in the haplotypes by using the multiplex haplotype analysis system used in the present study
with DNA sequence tags specific for the variants of all gene segments in this region
 
Publisher BioMed Central
 
Date 2011-01-27
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://neeri.csircentral.net/857/1/SreemantaBMCGenomics_2011.pdf
Pramanik , Sreemanta and Cui, Xiangfeng and Wang, Hui-Yun and Chimge, Nyam-Osor and Hu, Guohong and Shen, Li and Gao, Richeng and Li, Honghua (2011) Segmental duplication as one of the driving forces underlying the diversity of the human immunoglobulin heavy chain variable gene region. BMC Genomics, 12. ISSN 1471-2164
 
Relation https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-12-78
http://neeri.csircentral.net/857/