Oryctolagus cuniculus strain:New Zealand White Rabbit Targeted Locus (Loci)

Rabbits have been used extensively as a model system for the elucidation of the mechanism of immunoglobulin diversification and for the production of antibodies. We employed Next Generation Sequencing to analyze Ig germline V and J gene usage, CDR3 length and amino acid composition, and gene conversion frequencies within the functional (transcribed) IgG repertoire of the New Zealand white rabbit (Oryctolagus cuniculus). Several previously unannotated rabbit heavy chain variable (VH) and light chain variable (VL) germline elements were deduced bioinformatically using multidimensional scaling and k-means clustering methods. We estimated the gene conversion frequency in the rabbit at 23% of Ig sequences with a mean gene conversion tract length of 59±36 bp. Sequencing and gene conversion analysis of the chicken, human, and mouse repertoires revealed that gene conversion occurs much more extensively in the chicken (frequency 70%, tract length 79±57 bp), was observed to a small, yet statistically significant extent in humans, but was virtually absent in mice.

家兔已被广泛用作阐明免疫球蛋白多样性产生机制与抗体制备的模式生物系统。本研究采用下一代测序（Next Generation Sequencing）技术，分析了新西兰白兔（Oryctolagus cuniculus）功能性（转录型）IgG抗体库中的免疫球蛋白（Ig）胚系V、J基因使用偏好、CDR3（Complementarity Determining Region 3）长度与氨基酸组成，以及基因转换频率。本研究通过多维标度法与k均值聚类等生物信息学手段，推导获得了数个此前未被注释的家兔重链可变区（heavy chain variable, VH）与轻链可变区（light chain variable, VL）胚系序列元件。经估算，家兔的基因转换发生率约占免疫球蛋白序列的23%，平均基因转换片段长度为59±36碱基对（bp）。对鸡、人及小鼠抗体库开展的测序与基因转换分析结果显示，基因转换在鸡体内的发生更为广泛（发生率70%，平均片段长度79±57碱基对（bp）），在人体内仅存在少量但具有统计学显著性的基因转换现象，而在小鼠体内则几乎未检测到该现象。