Restricted V H Gene Usage and Generation of Antibody Diversity in Rabbit

Near-isogenic lines (NILs) are useful for plant genetic and genomic studies. However, the strength of conclusions from such studies depends on the similarity of the NILs’ genetic backgrounds. In this study, we investigated the genetic similarity for a set of NILs developed in the 1990s to study gene-for-gene interactions between wheat ( Triticum aestivum L.) and the Hessian fly ( Mayetiola destructor (Say)), an important pest of wheat. Each of the eight NILs carries a single H resistance gene and was created by successive backcrossing for two to six generations to susceptible T. aestivum ‘Newton’. We generated 256 target region amplification polymorphism (TRAP) markers and used them to calculate genetic similarity, expressed by the Nei and Li (NL) coefficient. Six of the NILs (H3, H5, H6, H9, H11, and H13) had the highly uniform genetic background of Newton, with NL coefficients from 0.97 to 0.99. However, genotypes with H10 or H12 were less similar to Newton, with NL coefficients of 0.86 and 0.93, respectively. Cluster analysis based on NL coefficients and pedigree analysis showed that the genetic similarity between each of the NILs and Newton was affected by both the number of backcrosses and the genetic similarity between Newton and the H gene donors. We thus generated an equation to predict the number of required backcrosses, given varying similarity of donor and recurrent parent. We also investigated whether the genetic residues of the donor parents that remained in the NILs were related to linkage drag. By using a complete set of ‘Chinese Spring’ nullisomic-tetrasomic lines, one third of the TRAP markers that showed polymorphism between the NILs and Newton were assigned to a specific chromosome. All of the assigned markers were located on chromosomes other than the chromosome carrying the H gene, suggesting that the genetic residues detected in this study were not due to linkage drag. Results will aid in the development and use of near-isogenic lines for studies of the functional genomics of wheat.

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Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis

Blood ◽

10.1182/blood-2007-07-099564 ◽

2008 ◽

Vol 111 (3) ◽

pp. 1524-1533 ◽

Cited By ~ 226

Author(s):

Fiona Murray ◽

Nikos Darzentas ◽

Anastasia Hadzidimitriou ◽

Gerard Tobin ◽

Myriam Boudjogra ◽

...

Keyword(s):

Amino Acid ◽

Chronic Lymphocytic Leukemia ◽

Heavy Chain ◽

Germ Line ◽

Somatic Hypermutation ◽

Lymphocytic Leukemia ◽

Chain Gene ◽

Distinctive Features ◽

Ighv Gene ◽

Gene Usage

Abstract Somatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, “stereotyped” amino acid changes occurred across the entire IGHV region in CLL subsets carrying stereotyped HCDR3 sequences, especially those expressing the IGHV3-21 and IGHV4-34 genes. These mutations are underrepresented among non-CLL sequences and thus can be considered as CLL-biased. Furthermore, it was shown that even a low level of mutations may be functionally relevant, given that stereotyped amino acid changes can be found in subsets of minimally mutated cases. The precise targeting and distinctive features of somatic hypermutation (SHM) in selected subgroups of CLL patients provide further evidence for selection by specific antigenic element(s).

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