We considered the possibility that the greater the distance between an immune receptor V and J, the more likely the V usage. Such a hypothesis is supported by results from mouse experiments. And, such a hypothesis is consistent with the fundamental nature of recombination and genomic distance: the further the distance, the greater the chance of a DNA break. Thus, we exploited the vast dataset of V and J recombination reads available for the human TRA gene, particularly from cancer and blood specimens, to assess the frequency of TRAV usage with respect to distance from the TRAJ cluster. Results indicated that, indeed, over the entire TRAV cluster, there is a greater chance of V usage the further the distance from the J cluster. These results do not address causation, and are not consistent for certain individual V gene segments, but the results do indicate that overall, the larger the distance between the V and J gene segment cluster, the more likely the appearance of at least a subset of TRAV segments, particularly among tumor infiltrating lymphocytes. With a similar approach, the distal TRAV gene segments were also found to be more commonly associated with a subset of distal TRAJ segments. These results have implications for restrictions on the apparent TRA repertoire in disease settings.

中文翻译：

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距TRAJ基因片段簇较远的TRAV基因片段在人类肿瘤和血液样本中更为常见。

我们考虑了免疫受体V和J之间的距离越大，V使用的可能性越大的可能性。小鼠实验的结果支持了这种假设。而且，这种假设与重组和基因组距离的基本性质一致：距离越远，DNA断裂的机会就越大。因此，我们利用了可用于人类TRA基因（尤其是癌症和血液样本）的V和J重组读数的庞大数据集，来评估TRAV使用频率相对于距TRAJ簇的距离。结果表明，实际上，在整个TRAV群集中，与J群集的距离越远，使用V的可能性就越大。这些结果并未解决因果关系，并且对于某些单个V基因片段而言并不一致，但结果确实表明，总​​体而言，V和J基因片段簇之间的距离越大，TRAV片段的至少一个子集出现的可能性就越大，尤其是在肿瘤浸润淋巴细胞中。用类似的方法，也发现远端TRAV基因区段与远端TRAJ区段的子集更普遍相关。这些结果暗示着对疾病环境中明显的TRA库的限制。