Mallon Ann-Marie, Wilming Laurens, Weekes Joseph, Gilbert James G R, Ashurst Jennifer, Peyrefitte Sandrine, Matthews Lucy, Cadman Matthew, McKeone Richard, Sellick Chris A, Arkell Ruth, Botcherby Marc R M, Strivens Mark A, Campbell R Duncan, Gregory Simon, Denny Paul, Hancock John M, Rogers Jane, Brown Steve D M
Medical Research Council Mammalian Genetics Unit, Harwell, Oxfordshire, United Kingdom.
Genome Res. 2004 Oct;14(10A):1888-901. doi: 10.1101/gr.2478604. Epub 2004 Sep 13.
Del(13)Svea36H (Del36H) is a deletion of approximately 20% of mouse chromosome 13 showing conserved synteny with human chromosome 6p22.1-6p22.3/6p25. The human region is lost in some deletion syndromes and is the site of several disease loci. Heterozygous Del36H mice show numerous phenotypes and may model aspects of human genetic disease. We describe 12.7 Mb of finished, annotated sequence from Del36H. Del36H has a higher gene density than the draft mouse genome, reflecting high local densities of three gene families (vomeronasal receptors, serpins, and prolactins) which are greatly expanded relative to human. Transposable elements are concentrated near these gene families. We therefore suggest that their neighborhoods are gene factories, regions of frequent recombination in which gene duplication is more frequent. The gene families show different proportions of pseudogenes, likely reflecting different strengths of purifying selection and/or gene conversion. They are also associated with relatively low simple sequence concentrations, which vary across the region with a periodicity of approximately 5 Mb. Del36H contains numerous evolutionarily conserved regions (ECRs). Many lie in noncoding regions, are detectable in species as distant as Ciona intestinalis, and therefore are candidate regulatory sequences. This analysis will facilitate functional genomic analysis of Del36H and provides insights into mouse genome evolution.
Del(13)Svea36H（Del36H）是小鼠13号染色体约20%的缺失，与人类6号染色体6p22.1 - 6p22.3/6p25区域存在保守的同线性。该人类区域在一些缺失综合征中丢失，并且是多个疾病基因座的所在位置。杂合的Del36H小鼠表现出众多表型，可能可模拟人类遗传疾病的某些方面。我们描述了来自Del36H的12.7 Mb完成注释的序列。Del36H的基因密度高于小鼠基因组草图，这反映了三个基因家族（犁鼻器受体、丝氨酸蛋白酶抑制剂和催乳素）的局部高浓度，这些基因家族相对于人类有极大的扩增。转座元件集中在这些基因家族附近。因此我们认为它们的邻域是基因工厂，即频繁重组的区域，其中基因复制更为频繁。这些基因家族显示出不同比例的假基因，可能反映了纯化选择和/或基因转换的不同强度。它们还与相对较低的简单序列浓度相关，该浓度在整个区域以约5 Mb的周期变化。Del36H包含众多进化保守区域（ECR）。许多位于非编码区域，在远至海鞘的物种中都可检测到，因此是候选调控序列。该分析将有助于对Del36H进行功能基因组分析，并为小鼠基因组进化提供见解。
