Gao Yu, Wahlberg Per, Marthey Sylvain, Esquerré Diane, Jaffrézic Florence, Lecardonnel Jérome, Hugot Karine, Rogel-Gaillard Claire
INRA, UMR 1313 de Génétique Animale et Biologie Intégrative, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
Vet Immunol Immunopathol. 2012 Jul 15;148(1-2):78-84. doi: 10.1016/j.vetimm.2011.04.007. Epub 2011 Apr 20.
The major histocompatibility complex (MHC) in Mammals is one of the most gene dense regions of the genome and contains the polymorphic histocompatibility gene families known to be involved in pathogen response and control of auto-immunity. The MHC is a complex genetic system that provides an interesting model system to study genome expression regulation and genetic diversity at the megabase scale. The pig MHC or SLA (Swine Leucocyte Antigen) complex spans 2.4 megabases and 151 loci have been annotated. We will review key results from previous RNA expression studies using microarrays containing probes specific to annotated loci within SLA and in addition present novel data obtained using high-density tiling arrays encompassing the whole SLA complex. We have focused on transcriptome modifications of porcine peripheral blood mononuclear cells stimulated with a mixture of phorbol myristate acetate and ionomycin known to activate B and T cell proliferation. Our results show that numerous loci mapping to the SLA complex are affected by the treatment. A general decreased level of expression for class I and II genes and an up-regulation of genes involved in peptide processing and transport were observed. Tiling array-based experiments contributed to refined gene annotations as presented for one SLA class I gene referred to as SLA-11. In conclusion, high-density tiling arrays can serve as an excellent tool to draw comprehensive transcription maps, and improve genome annotations for the SLA complex. We are currently studying their relevance to characterize SLA genetic diversity in combination with high throughput next generation sequencing.
哺乳动物的主要组织相容性复合体（MHC）是基因组中基因密度最高的区域之一，包含已知参与病原体应答和自身免疫控制的多态性组织相容性基因家族。MHC是一个复杂的遗传系统，为研究兆碱基规模的基因组表达调控和遗传多样性提供了一个有趣的模型系统。猪的MHC或SLA（猪白细胞抗原）复合体跨度为2.4兆碱基，已注释了151个基因座。我们将回顾以往使用含有针对SLA内注释基因座的特异性探针的微阵列进行的RNA表达研究的关键结果，此外还将展示使用涵盖整个SLA复合体的高密度平铺阵列获得的新数据。我们重点研究了用佛波酯肉豆蔻酸酯乙酸盐和离子霉素混合物刺激猪外周血单核细胞后的转录组修饰，已知该混合物可激活B细胞和T细胞增殖。我们的结果表明，许多定位到SLA复合体的基因座受到该处理的影响。观察到I类和II类基因的表达水平普遍下降，以及参与肽加工和转运的基因上调。基于平铺阵列的实验有助于完善基因注释，如针对一个称为SLA-11的SLA I类基因所呈现的那样。总之，高密度平铺阵列可作为绘制全面转录图谱以及改善SLA复合体基因组注释的优秀工具。我们目前正在研究它们与结合高通量下一代测序来表征SLA遗传多样性的相关性。
