Groningen Bioinformatics Centre, University of Groningen, 9751 NN, Haren, The Netherlands.
Genetics. 2010 Sep;186(1):405-10. doi: 10.1534/genetics.110.119677. Epub 2010 Jul 6.
Alternative splicing is considered a major mechanism for creating multicellular diversity from a limited repertoire of genes. Here, we performed the first study of genetic variation controlling alternative splicing patterns by comprehensively identifying quantitative trait loci affecting the differential expression of transcript isoforms in a large recombinant inbred population of Caenorhabditis elegans, using a new generation of whole-genome very-high-density oligonucleotide microarrays. Using 60 experimental lines, we were able to detect 435 genes with substantial heritable variation, of which 36% were regulated at a distance (in trans). Nonetheless, we find only a very small number of examples of heritable variation in alternative splicing (22 transcripts), and most of these genes colocalize with the associated genomic loci. Our findings suggest that the regulatory mechanism of alternative splicing in C. elegans is robust toward genetic variation at the genome-wide scale, which is in striking contrast to earlier observations in humans.
可变剪接被认为是从有限的基因库中创建多细胞多样性的主要机制。在这里，我们通过全面鉴定影响大型秀丽隐杆线虫重组近交系群体中转录本亚型差异表达的数量性状基因座，首次研究了控制可变剪接模式的遗传变异，使用新一代全基因组超高密度寡核苷酸微阵列。使用 60 条实验品系，我们能够检测到 435 个具有显著遗传变异的基因，其中 36%是远距离调控（顺式调控）。尽管如此，我们只发现了少数遗传可变剪接的例子（22 个转录本），而且大多数这些基因与相关的基因组座共定位。我们的研究结果表明，秀丽隐杆线虫中可变剪接的调控机制在全基因组范围内对遗传变异具有稳健性，这与人类早期的观察结果形成鲜明对比。
