Organization of variable region segments of the human immunoglobulin heavy chain: duplication of the D5 cluster within the locus and interchromosomal translocation of variable region segments.

Abstract

We have studied the organization of variable region (V) genes of the human immunoglobulin heavy chain (H) by cosmid cloning. We isolated two independent immunoglobulin D5 clusters (D5‐a and D5‐b) from cosmid libraries of the human genome. Restriction maps of these two regions showed that downstream 15 kb portions of the 55 kb overlap were different although upstream 40 kb portions were almost identical. Four more D segments, (DM, DXP, DA and DK) were found around the D5 segment in the conserved region of each cluster. Nucleotide sequences of the corresponding D segments from each cluster were almost identical and they encoded potentially functional D regions. Analysis using human‐rodent somatic cell hybrids demonstrated that both clusters were located in the immunoglobulin heavy chain (H) locus on chromosome 14, suggesting that the D5‐a and D5‐b regions evolved by internal duplication within this locus. We also isolated a 60 kb DNA region carrying four VH segments, designated as VH‐F region, which was located on chromosome 16. Nucleotide sequences of the four VH segments were determined. Two of them encoded potentially functional VH segments, and the other two were pseudogenes. Some more VH segments were found to be located outside chromosome 14, by Southern blot hybridization of human‐rodent hybrid cell DNAs. These results provide further evidence that the human VH locus has undergone recent reorganization.

Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response

“…[22][23][24][25][26][27] For inclusion in this study it was necespost-induction, respectively, of causes related to therapy in sary that patients entered clinical and morphological clinical remission, all patients have been followed for у24 remission and that samples were PCR positive for amplifimonths or have relapsed earlier. Relapsed patients had a cation of the ␤-actin control sequence.…”

Determination of gene organization in the human IGHV region on single chromosomes

“…The human IGHV genes map to three chromosomes: chromosome 14, 1-3 chromosome 15, 4 and chromosome 16. 5,6 However, only the IGHV locus on chromosome 14 is essential for somatic generation of the IGH gene coding for the heavy chain. Mapping and sequencing efforts from different laboratories have contributed to understanding the physical structure of the IGHV region.…”

Immunoglobulin Polygeny: An Evolutionary Perspective

“…2B). The same phenomenon occurs in the VH sublocus of mice (Retter et al, 2007;Johnston et al, 2006) humans (Matsuda et al, 1990) and in swine (Eguchi-Ogawa et al, 2010). For example, the genomic segment in swine that contains VHA, VHB and VHE has been duplicated to yield VHA*, VHB* and VHF.…”

“…1B). A striking feature of IGSF genes that encode the variable region domain of Igs is the degree of polygeny such that duplicated VH genes alone can occupy > three megabases (Matsuda et al, 1990). There are three such variable region loci in mammals: VH, Vλ and Vκ.…”

“…1A) while Vλ and Vκ encode the light chains variable region domains. All three loci are independent (non-linked) although a few orphan human VH genes can be found in other linkage groups (Matsuda et al, 1990). Popular textbooks suggest that this polygeny explains why antibodies can recognize >10 10 different antigens.…”