PDF(Pubmed)
Abstract：
Leukocyte immunoglobulin (Ig)-like receptors (LILRs) on human chromosome 19q13.4 encode 11 immunoglobulin superfamily receptors, exhibiting genetic diversity within and between human populations. Among the LILR genes, the genomic region surrounding LILRB3 and LILRA6 has yet to be fully characterized due to their significant sequence homology, which makes it difficult to differentiate between them. To examine the LILRB3 and LILRA6 genomic region, a tool named JoGo-LILR CN Caller, which can call copy number from short-read whole genome sequencing (srWGS) data, was applied to an extensive international srWGS dataset comprising 2,504 samples. During this process, a previously unreported loss of both LILRB3 and LILRA6 was detected in three samples. Using long-read sequencing of these samples, we have discovered a novel large deletion (33,692 bp) in the LILRB3 and LILRA6 genomic regions in the Japanese population. This deletion spanned three genes, LILRB3, LILRA6, and LILRB5, resulting in LILRB3 exons 12-13 being located immediately downstream of LILRB5 exons 1-12 with the loss of LILRA6, suggesting the potential expression of a hybrid gene between LILRB5 and LILRB3 (LILRB5-3). Transcription and subsequent translation of the LILRB5-3 hybrid gene were also verified. The hybrid junction was located within the intracellular domain, resulting in an LILRB5 extracellular domain fused to a partial LILRB3 intracellular domain with three immunoreceptor tyrosine-based inhibitory motifs (ITIMs), suggesting that LILRB5-3 acquired a novel signaling function. Further application of the JoGo-LILR tool to srWGS samples suggested the presence of the LILRB5-3 hybrid gene in the CEU population. Our findings provide insight into the genetic and functional diversity of the LILR family.
摘要：
人类染色体19q13.4上的白细胞免疫球蛋白（Ig）样受体（LILRs）编码11个免疫球蛋白超家族受体，在人群内部和人群之间表现出遗传多样性。在LILR基因中,LILRB3和LILRA6周围的基因组区域由于其显著的序列同源性而尚未被完全表征，这使得很难区分它们。为了检查LILRB3和LILRA6基因组区域，一个名为JoGo-LILRCNCaller的工具，可以从短阅读全基因组测序（srWGS）数据中调用拷贝数，应用于包含2,504个样本的广泛的国际srWGS数据集。在这个过程中,在3个样本中检测到以前未报告的LILRB3和LILRA6丢失.使用这些样本的长读数测序，我们在日本人群的LILRB3和LILRA6基因组区域中发现了一个新的大缺失（33,692bp）。这个缺失跨越了三个基因，LILRB3，LILRA6和LILRB5，导致LILRB3外显子12-13位于LILRB5外显子1-12的下游，而LILRA6的丢失，表明LILRB5和LILRB3（LILRB5-3）之间的杂合基因的潜在表达。还验证了LILRB5-3杂合基因的转录和随后的翻译。杂合连接位于胞内结构域内，导致LILRB5胞外结构域与具有三个免疫受体基于酪氨酸的抑制基序（ITIM）的部分LILRB3胞内结构域融合，表明LILRB5-3获得了一种新的信号功能。将JoGo-LILR工具进一步应用于srWGS样品表明CEU群体中存在LILRB5-3杂合基因。我们的发现为LILR家族的遗传和功能多样性提供了见解。
